The performance of polyamide nanofiltration membrane for long-term operation inan integrated membran

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仿制药晶型研究的技术指导原则英文

仿制药晶型研究的技术指导原则英文Technical Guidance Principles for the Study of Generic Drug Polymorphs1. Comprehensive Literature Review:Conduct a thorough review of existing literature on the polymorphic forms of the reference drug substance. Identify the different polymorphs reported and their characterization methods, including X-ray diffraction, thermal analysis, and spectroscopic techniques.2. Sample Preparation:Ensure that the sample preparation technique maintains the integrity and purity of the reference drug substance. Use appropriate methods such as crystallization, recrystallization, or solvent evaporation to obtain the desired polymorphs for characterization.3. Controlled Crystallization Conditions:Conduct crystallization experiments under controlled conditions to promote the formation of specific polymorphs. Factors such as temperature, solvent selection, cooling rate, and agitation should be considered and optimized to achieve reproducible results.4. Polymorph Characterization:Employ a combination of analytical techniques to characterize the obtained polymorphs. X-ray diffraction is essential to confirm the crystalline nature and determine the crystal structure. Use thermal analysis techniques such as differential scanning calorimetry and thermogravimetric analysis to investigate thermal behavior. Complement these techniques with spectroscopic tools like infrared spectroscopy and solid-state nuclear magnetic resonance to confirm structural differences.5. Physical Property Comparison:Compare the physical properties (e.g., melting point, solubility, density) of the newly formed polymorphs with those of the reference drug substance. Any significant differences may indicate a new polymorphic form.6. Stability Studies:Conduct stability studies to evaluate the stability of the polymorphs under different environmental conditions, including temperature, humidity, and light exposure. Monitor changes in physical properties and assess any potential degradation or transformation.7. Bioavailability Studies:Perform bioavailability studies to determine if the newly formedpolymorphs exhibit similar or improved bioavailability compared to the reference drug substance. In vitro dissolution testing and in vivo pharmacokinetic studies can provide valuable insights into the drug's performance.8. Regulatory Compliance:Ensure that the research and development of generic drug polymorphs adhere to applicable regulatory guidelines, such as those set by the Food and Drug Administration (FDA) or European Medicines Agency (EMA). Demonstrate the equivalence or superiority of the polymorphs through rigorous scientific evidence.9. Documentation and Reporting:Maintain detailed records of all experimental procedures, data, and observations. Prepare comprehensive reports that summarize the research findings and provide sufficient evidence to support the conclusions drawn.10. Intellectual Property Considerations:Respect existing patents and intellectual property rights when conducting research on generic drug polymorphs. Ensure compliance with applicable legal requirements and consider seeking legal advicewhen necessary.Note: It is important to consult specific guidelines and requirements from regulatory authorities or professional organizations when conducting research on generic drug polymorphs.。

静电纺丝素纳米纤维敷料对大鼠深Ⅱ度烧伤创面HIF-1α和PCNA表达的影响

文章编号：1007—4287(2020)09— 1544— 05静电纺丝素纳米纤维敷料对大鼠深I I度烧伤创面HIF-l a和PCNA表达的影响沙娜，陈华'刘宁，单爱军，刘海华(深圳市人民医院（暨南大学第二临床医学院，南方科技大学第一附属医院）急诊科.广东深圳518020)摘要：目的观察静电纺丝素纳米纤维敷料对大鼠深11度烧伤创面组织中缺氧诱导因子-l a(H l F-l a)和增殖细胞核抗原（P C N A)表达的影响，探讨静电纺丝素纳米纤维敷料对大鼠深I I度烧伤创面愈合的作用及吋能机制。

方法选取60只健康雄性SI)大鼠作为受试对象，建立大鼠深I I度烧伤模型，随机分成实验组和空白对照组，分别用静电纺丝素纳米纤维敷料和生理盐水纱布敷料徵盖烧伤创面治疗。

分别于烫伤后第3、7、14、21天观察两组大鼠的创面愈合情况，并切取创面组织•通过苏木精-伊红（H E)染色和M a s s o n染色观察创面组织病理学变化情况，免疫组化法(I H C)检测创面组织内H I F-l a和P C N A的阳性细胞表达变化情况。

结果烫伤后第3、7、14、21天观察到两组大鼠创面逐渐缩小，愈合率逐渐升高，与对照组相比较，实验组创面愈合时间缩短，创面愈合率升高（P<〇. 〇5),创面组织中H I F-l a阳性表达细胞数量减少，P C N A阳性表达细胞数量增加。

结论静电纺丝素纳米纤维敷料能够下调HI F l a和上调P C N A表达水平，具有促进大鼠深I I度烫伤创面愈合的作用•其机制可能与改善创面局部缺氧状态和促进细胞增殖有关。

关键词：静电纺丝素纳米纤维；烧伤；缺氧诱导因子增殖细胞核抗原；创面愈合中图分类号：R644 文献标识码：AEffect of electrospun silk fibroin nanofibers on the expression of H IF-la and PCNA in deep second degree burn wounds in rats S H A N a9C H E N H ua ^L I U Nijifi ,et a l. (,D epartment o f Emerge?icy ^Shenzhen P eople \s H o s p ita li The Second Clinical M edical College ,J inati U niversity ; The First A f f i l i a t e d H o s p ita l ^Southern U niv ersity o f Science and Techn o lo g y) * S he nzhe n b\S020<,Chi ?ia)A bstract：Objective T o observe the effect of electrospun silk fibroin nanofibers d ressin g on the expression of hypoxia inducible fa c to r-la(H I F-la)and proliferating cell nuclear antigen (P C N A) in deep second degree burn w ound tivssues of rats. T o explore the effect and possible m echanism of electrospun silk fibroin nanofiber dressing on deep second-degree bu rn w ound healing in rats. Methods Sixty healthy m ale SD rats w ere selected as subjects to establish a rat m odel of deep second-degree b urns. T h ey w ere random ly divided into experim ental gro u p and blank control group. T he burn w ounds w ere covered w ith electrospun silk fibroin nanofibers d ressing and saline gauze dressing respectively. T he w ound healing of the tw o gro up s of ra ts w as observed on the 3rd, 7th, 14th, and 21st clays a fte r sc a ld.an d the w ound tissue was cut o u t,a n d the pathological changes of the w ound w ere observed by hem atoxylin-eosin (H K) staining and M asson vStaining. Im m unohistochem istry (IH C) w as used to detect changes in the expressio n of H IF-la and PC N A positive cells in the w ound tissue. Results O n the 3r d,7th. 14th,a n d21st days a fte r sc a ld,th e w ounds of the tw o group.s of ra ts w ere observed to g radually sh rink and the healing rate gradually increased. C om pared w ith the control g ro u p, the w ound healing tim e of the experim ental group w as .shortened, and the w ound healing rate increased (P<C0. 05), the num ber of H IF-la positive cells in the w ound tissu e d ecreased.and the num ber of P C N A-posilive cells increased. Conclusion E lectrosp u n silk fibroin nanofibers d ressing can dow n-regulate H IF-la exprcSvsion. up-regulate the expression of PCN A, and p rom ote the healing of deep second-degree scalds in rats. T h e m echanism m ay be related to im proving the local hypoxia sta te of the w ound and prom oting cell proliferation.Key w ords：electrospjun silk fibroin n a n o fib ers；burn ；H IF-1 a; PC'NA ；w ound healing(C h i n J L a b»2020 *24 ： 1544)基金项目：深圳市科技创新委员会科技计划项目（.丨CYJ20170307100 359390)静电纺丝素纳米纤维是将桑蚕丝运用静电纺丝技术制备的纳米级分子纤维，具有高比表面积、高孔隙率、良好的生物组织相容性等优点，因而在生物医*通讯作者学等领域中得到广泛研究，尤其是在组织工程皮肤、创面修复等方面具有广阔的应用潜力[1]。

纤维素模板法制备多孔碳纳米棒及其超级电容器性能(英文)

Porous carbons have potential applications in rubber additives，gas separation，catalysis and energystorage［1］． For a variety of practical applications，the fabrication of desired morphologies is important as well as the control of composition，structure and porosity． Herein we report the facile fabrication of porous carbon nanorods based on atom transfer radical polymerization （ ATＲP ） process by using cellulose brushes as template． The schematic procedure for the preparation of porous carbon nanorods was shown in Fig 1． The fabrication of porous carbon nanorods was schematically illustrated in Fig 1． Cellulose was completely dissolved in ionic liquid to form homogeneous solution using 1-allyl-3-methylimidazolium chloride as the solvent ［Fig 1 （ a）］［2］． Then cellulose-macroinitiator was prepared by esterification using 2-bromoisobutyryl bromide［Fig 1（ b）］． Cellulose-g-polyacrylonitrile（ cellulose-g-PAN） brushes were synthesized by ATＲP method ［Fig 1（ c）］，followed by thermal stabilization and carbonization under nitrogen atmosphere to obtain the nanostructured carbonrods［Fig 1 （ d）］．

静电纺丝法固态聚合物电解质

静电纺丝法固态聚合物电解质英文回答：Electrospinning is a versatile technique that has been widely used to produce nanofibers from various materials. One of the applications of electrospinning is in the fabrication of solid-state polymer electrolytes. Solid-state polymer electrolytes are materials that exhibit both the mechanical properties of a solid and the ionic conductivity of a liquid electrolyte. They have attracted significant attention due to their potential applicationsin energy storage devices such as lithium-ion batteries and fuel cells.The electrospinning process involves the use of a high voltage to create an electric field between a polymer solution and a collector. When the electric field is applied, the polymer solution forms a Taylor cone at thetip of a spinneret. As the electric field strength increases, a jet of polymer solution is ejected from theTaylor cone and elongates due to the electrostatic forces. During the flight of the jet, the solvent evaporates, and the polymer solidifies, resulting in the formation of nanofibers. These nanofibers can then be collected to form a non-woven mat or other desired structures.Solid-state polymer electrolytes can be obtained by electrospinning a polymer solution containing a suitable ionic salt. The ionic salt dissociates into cations and anions, which are then immobilized within the polymer matrix. The presence of the ionic salt enhances the ionic conductivity of the polymer electrolyte. Additionally, the high surface area-to-volume ratio of the electrospun nanofibers provides a large contact area for ion transport, further improving the overall conductivity.One advantage of using electrospinning to fabricate solid-state polymer electrolytes is the ability to control the morphology and structure of the resulting nanofibers. By adjusting the electrospinning parameters such as the polymer concentration, applied voltage, and spinning distance, the diameter and alignment of the nanofibers canbe tailored. This control over the nanofiber morphology can significantly influence the performance of the polymer electrolyte in terms of mechanical strength, ion transport, and electrochemical stability.In addition to their excellent mechanical and electrochemical properties, solid-state polymerelectrolytes produced by electrospinning also offer the advantage of flexibility. The nanofiber-based structure allows the electrolyte to be easily integrated intoflexible and thin film devices, enabling the development of flexible energy storage systems. This flexibility is particularly desirable in applications where conformability and lightweight are crucial, such as wearable electronics and portable power sources.中文回答：静电纺丝是一种多功能的技术，被广泛用于制备各种材料的纳米纤维。

一种噻吩基双偶极半菁与普鲁士蓝的静电自组装薄膜

一种噻吩基双偶极半菁与普鲁士蓝的静电自组装薄膜王志平;罗虹;高丽华;王科志【摘要】We successfully prepared a novel inorganic-organic hybrid electrostatically self-assembled multilayer film by alternately depositing Prussian blue (PB) and a thiophene-containing hemicyanine. The optical, electrochemical, and photoelectrochemical properties of the as-prepared films were studied by UV-visible absorption spectroscopy, cyclic voltammetry, and photoelectrochemical experiment. Linear increases in the absorbances at 376 and 698 nm with the number of deposited layers, up to at least 8 layers, indicated that film deposition was uniform and reproducible. The PB in the prepared films was found to occur surface-confined rather than diffusion-controlled redox reactions and the peak currents increased with an increase in the number of layers up to 5 layers. Upon irradiation with 100 mW· cm-2 white light the films exhibited stable and reproducible cathodic photocurrents, which increased as the number of layers increased up to 4 layers. A maximum photocurrent density of 0.28 μA· cm-2 was found for the four-layer film at a bias voltage of -0.4 V vs the saturated calomel electrode.%通过交替沉积普鲁士蓝和一种含噻吩的半菁,制备了一种新的无机-有机杂化静电自组装膜.用紫外-可见吸收光谱、循环伏安技术和光电化学实验对薄膜进行了表征或光电性质研究.376和698 nm处薄膜的吸光度随薄膜层数增加线性增加,表明薄膜的沉积是均匀和可重复的.薄膜中的普鲁士蓝具有良好的表面控制而非扩散控制的电化学活性.膜的层数从1增加至5时,阳极峰电流随膜层数增加而线性增加.100 mW·cm-2的白光照射下,薄膜产生稳定的阴极光电流,随层数增加线性增长,层数增加到4层时,光电流达到最大值.饱和甘汞电极为参比电极,-0.4 V偏压下,4层薄膜产生的光电流密度高达0.28 μA·cm-2.【期刊名称】《物理化学学报》【年(卷),期】2011(027)003【总页数】5页(P754-758)【关键词】半菁;自组装膜;循环伏安;紫外可见光谱;噻吩;光电化学性质【作者】王志平;罗虹;高丽华;王科志【作者单位】北京师范大学化学学院,北京100875;集宁师范学院,内蒙古集宁012000;北京师范大学化学学院,北京100875;北京工商大学化学与环境工程学院,北京100048;北京师范大学化学学院,北京100875【正文语种】中文【中图分类】O646Abstract: We successfully prepared a novel inorganic-organic hybrid electrostatically self-assembled multilayer film by alternately depositing Prussian blue(PB)and a thiophene-containing hemicyanine.Theoptical,electrochemical,and photoelectrochemical properties of the as-prepared films were studied by UV-visible absorption spectroscopy,cyclic voltammetry,and photoelectrochemical experiment.Linear increases in the absorbances at 376 and 698 nm with the number of deposited layers,up to at least 8 layers,indicated that film deposition was uniform and reproducible.The PB in the prepared films was found to occur surface-confined rather than diffusion-controlled redox reactions and the peak currents increased with an increase in the number of layers up to 5 layers.Upon irradiation with 100 mW·cm-2white light the films exhibited stable and reproducible cathodic photocurrents,which increased as the number of layers increased up to 4 layers.A maximum photocurrent density of 0.28 μA·cm-2was found for the four-layer film at a bias voltage of-0.4 Vvsthe saturated calomel electrode.Key Words:Hemicyanine;Self-assembled film;Cyclic voltammetry;UV-visible spectrum;Thiophene;Photoelectrochemical propertyDecher1发展的以静电作用力为驱动、将阴阳离子交替沉积吸附制备自组装膜的技术,由于具有方法简单、厚度可控、性质稳定和高度的分子水平组装能力的特点,已引起科学工作者的广泛关注,而有机-无机杂化材料的静电自组装膜已成为目前研究的热点.2,3半菁化合物是备受关注的二阶非线性光学和光电转换材料,过去的十几年的时间里主要采用Langmuir-Blodgett(LB)技术制备多层薄膜,4-10但LB技术具有仪器昂贵、制备费时和薄膜不够稳定等缺点.近年我们曾报道了双偶极半菁和Ru(II)配合物与杂多/同多阴离子、普鲁士蓝和WO3形成的静电自组装多层薄膜,表现出诱人的二阶非线性光学性质和光电转换性质.11-19噻吩是重要的导电聚合物单体,在发光二极管、太阳能电池和场效应晶体管领域有重要应用前景.20普鲁士蓝是一类重要的电致变色、传感和磁学材料.21-24但含噻吩的半菁静电自组装膜未见文献报道.本文报道一种含噻吩基的新双偶极半菁衍生物与普鲁士蓝形成的静电自组装膜以及薄膜的氧化还原和光电化学性质,旨在为这种原料易得、制备简单的有机-无机复合的纳米薄膜材料在多领域的应用提供重要的基础实验数据.用于成膜的含噻吩基双偶极半菁(分子结构示于图1,简记为ABr2),按文献5,11报道的方法合成,经元素分析和核磁共振谱表征.普鲁士蓝{KFeIII4[FeII(CN)6]3}(简记为KFeIII-FeII)按文献14报道的方法合成.GBC Cintra 10e型紫外-可见分光光度计(澳大利亚);pHS3酸度计(上海精密科学仪器有限公司);CHI420电化学分析仪(上海辰华仪器公司);采用三电极系统,覆盖有自组装膜的氧化铟-氧化锡(ITO)玻璃为工作电极,铂丝为对电极,饱和甘汞电极为参比电极,支持电解质为0.5 mol·L-1的Na2SO4溶液(pH=1.93).白光光源(光强为100 mW·cm-2)为配有红外和紫外截止滤光片的500 W高压氙灯光源系统(北京畅拓科技有限公司),薄膜光照的有效面积为0.28 cm2.将石英和玻璃基片分别用98%浓硫酸:30%双氧水(体积比为3:1)和25%氨水:30%双氧水:水(体积比为1:1:5)清洁和亲水处理;ITO玻璃用氢氧化钠的饱和乙醇溶液清洁和亲水处理.处理后的石英和ITO基片按图2所示的途径途组装薄膜.首先按文献3,7,8方法进行表面硅烷化和氨基质子化,然后依次分别浸入1.0 mmol·L-1普鲁士蓝水溶液30 min和1.0 mmol·L-1ABr2水溶液50 min,每次取出后用pH=3.0的去离子水冲洗干净,空气吹干;重复图2所示的步骤2、3即可得到静电自组装多层膜.普鲁士蓝水溶液、半菁ABr2水溶液和9层[(FeIII-FeII)-/A2+]9膜的紫外-可见吸收光谱的比较如图3所示.从图中可见,ABr2在378 nm处出现了1个π→π*吸收峰,4普鲁士蓝在684 nm处出现了Fe(II)与Fe(III)间的电荷转移跃迁吸收峰,25而自组装多层膜在376和698 nm处明显出现了两个最大吸收峰,其中376 nm处的吸收峰和ABr2水溶液的吸收特征相似,698 nm处的吸收峰与普鲁士蓝的吸收特征相似,说明阴阳离子已组装到基片上.值得注意的是薄膜的吸收峰较普鲁士蓝发生了近14 nm的红移,可能源于膜中A2+与普鲁士蓝间发生电荷转移.21图4为不同层数[(FeIII-FeII)-/A2+]n(n=1-8)膜的紫外可见吸收光谱.从图中可见,不同层数的薄膜的吸收峰基本保持不变,表明层间分子的相互作用不随膜层数的增加而变化;在376和698 nm处的吸光度随着膜层数的增加而线性增加(见图4插图),表明两种成膜组分已被成功组装上去,且薄膜的沉积是均匀和可重复的.因为基片的两面均有膜,由376 nm处的吸光度随层数增加的直线斜率0.00576除以2,可得出单层膜[(FeIII-FeII)-/A2+]1膜的吸光度A=2.9×10-3,由ABr2水溶液在376 nm处的摩尔消光系数ε=5.4×104L·mol-1·cm-1,根据朗伯-比耳定律可推出半菁分子表面覆盖率Γ=10-3A/ε,其中A为每层的吸光度,ε为ABr2水溶液的摩尔消光系数.求得Γ=5.3×10-11mol·cm-2,此值大于我们最近报道的双核钌配合物与普鲁士蓝形成的静电自组装膜的表面覆盖率3.7×10-11mol·cm-2,14表明薄膜的致密性较好.同理,由在698 nm处单层膜的吸光度值4.0×10-3以及普鲁士蓝水溶液的摩尔消光系数值3.0×104L·mol-1·cm-1,求得普鲁士蓝在膜中的表面覆盖率为1.3×10-10mol·cm-2,约为半菁分子表面覆盖率值的2.5倍.显然,成膜材料的分子体积是控制每个成膜组分多少的关键因素,另外膜中组分间的电荷转移通常也是导致膜中组分非整比的因素.图5为以覆盖有4层[(FeIII-FeII)-/A2+]4膜的ITO基片为工作电极,饱和甘汞电极为参比电极,铂丝为对电极,电解液为0.5 mol·L-1的Na2SO4溶液(pH=1.93),在60-200 mV·s-1的扫描速率下的循环伏安曲线.可见薄膜分别在半波电位E1/2=0.015和0.97 V处出现两对氧化还原峰,可分别指认为如方程(1)和(2)所示普鲁士蓝PB被还原为Everitt盐ES(过程I)和PB被氧化为普鲁士黄PY(过程II)的两个过程:26如图5内插图所示,峰电流与扫描速率成正比,表明为表面控制而非扩散控制的氧化还原过程.图6为不同层数薄膜[(FeIII-FeII)-/A2+]n(n=1,2,3,5)的循环伏安曲线.由图6及其插图所示,膜的层数从1增加到5时,普鲁士蓝在膜中的氧化还原反应阳极峰电流随膜层数增加而线性增加.如图7(A)所示,-0.4 V偏压下,100 mW·cm-2白光照射2层薄膜[(FeIII-FeII)-/A2+]2产生较为稳定的阴极光电流,光电流达37 nA,明显有别于没有沉积薄膜的空白ITO电极产生的可忽略的微弱光电信号,可证实光电信号来自组装的薄膜.但光电流信号强度较我们最近研究的几种光电化学体系产生的光电流低.14,15,18可能源于本文研究的半菁吸光能力较差.偏压对光电流的影响研究表明,偏压越负,光电流越大,进一步证实为阴极光电流.薄膜产生的阴极光电流随膜层数增加而增加(光电流密度可达0.28 μA·cm-2),膜层数达4层后进一步增加层数,光电流减小(图7(B)). 紫外-可见吸收光谱、循环伏安技术和光电化学实验表明,能成功地通过静电自组装技术制备含有新型噻吩双偶极半菁和普鲁士蓝的多层超薄膜.薄膜在376和698 nm处的吸光度随着膜层数的增加而线性增加,测得膜中半菁和普鲁士蓝的表面覆盖率分别为5.3×10-11和1.3×10-10mol·cm-2,表明薄膜沉积均匀致密.循环伏安实验观察到两对分别指认为普鲁士蓝PB被还原为Everitt盐和PB被氧化为普鲁士黄的两对氧化还原峰,氧化还原过程为表面控制,且峰电流随层数增加而增加.白光照射下,薄膜能产生稳定的阴极光电流,4层薄膜的光电流密度可达0.28 μA·cm-2.【相关文献】(1) Decher,G.Science 1997,277,1232.(2)Zhang,X.;Chen,H.;Zhang,mun.2007,1395.(3)Wang,K.Z.;Gao,L.H.Mater.Res.Bull.2002,37,2447.(4)Lang,A.D.;Zhai,J.;Huang,C.H.;Gan,L.B.;Zhao,Y.L.;Zhou,D.J.;Chen,Z.D.J.Phys.Chem.B 1998,102,1424.(5)Yao,Q.H.;Shan,L.;Li,F.Y.;Yin,D.D.;Huang,C.H.Acta Phys.-Chim.Sin.2003,19,635.[姚巧红,单路,李富有,尹冬冬,黄春辉.物理化学学报,2003,19,635.](6)Wang,K.Z.;Huang,C.H.;Xu,G.X.;Xu,Y.;Liu,Y.Q.;Zhu,D.B.;Zhao,X.S.;Xie,X.M.;Wu.N.Z.Chem.Ma ter.1994,6,1986.(7)Wang,K.Z.;Huang,C.H.;Xu,G.X.;Zhao,X.S.;Xia,X.H.;Wu,N.Z.;Xu,L.G.;Li,T.K.Thin Solid Films 1994,252,139.(8)Wang,K.Z.;Huang,C.H.;Xu,G.X.;Wang,R.J.Polyhedron 1995,14,3669.(9)Wang,K.Z.;Jiang,W.;Huang,C.H.;Xu,G.X.;Xu,L.G.;Li,T.K.;Zhao,X.S.;Xie,X.M.Chem.Lett.1995,1 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磷酸酯己内酯

Functionalized micelles from block copolymer of polyphosphoester and poly(ɛ-caprolactone)for receptor-mediated drug deliveryYu-Cai Wang a,1,Xi-Qiu Liu b,1,Tian-Meng Sun b ,Meng-Hua Xiong a ,Jun Wang a,b,⁎aDepartment of Polymer Science and Engineering,University of Science and Technology of China,Hefei,Anhui 230026,PR ChinabHefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences,University of Science and Technology of China,Hefei,Anhui 230027,PR ChinaReceived 23October 2007;accepted 29January 2008Available online 16February 2008AbstractCellular specific micellar systems from functional amphiphilic block copolymers are attractive for targeted intracellular drug delivery.In this study,we developed reactive micelles based on diblock copolymer of poly(ethyl ethylene phosphate)and poly(ɛ-caprolactone).The micelles were further surface conjugated with galactosamine to target asialoglycoprotein receptor (ASGP-R)of HepG2cells.The size of micellar nanoparticles was about 70nm in diameter,and nanoparticles were negatively charged in aqueous solution.Through recognition between galactose ligands with ASGP-R of HepG2cells,cell surface binding and internalization of galactosamine-conjugated micelles were significantly promoted,which were demonstrated by flow cytometric analyses using rhodamine 123fluorescent dye.Paclitaxel-loaded micelles with galactose ligands exhibited comparable activity to free paclitaxel in inhibiting HepG2cell proliferation,in contrast to the poor inhibition activity of micelles without galactose ligands particularly at lower paclitaxel doses.In addition,population of HepG2cells arrested in G2/M phase was in positive response to paclitaxel dose when cells were incubated with paclitaxel-loaded micelles with galactosamine conjugation,which was against the performance of micelles without galactose ligand,owing to the ligand –receptor interaction.The surface functionalized micellar system is promising for specific anticancer drug transportation and intracellular drug release.©2008Elsevier B.V .All rights reserved.Keywords:Polyphosphoester;Biodegradable block copolymer;Receptor-mediated drug delivery;Reactive micelle;HepG2cells1.IntroductionDrug delivery systems using soluble polymers,liposomes,and self-assembled nanoparticles etc.have been developed to reduce the side effects and increase the therapeutic efficacy of anticancer drugs [1–4].Among them,loading drug molecules into the hydrophobic core of self-assembled polymer micelles in a mesoscopic size range (several tens of nanometers)is one of the resolutions to increase solubility of hydrophobic drug.Such micellar nanoparticles passively accumulate in solid tumortissues via enhanced permeability and retention (EPR)effect and enhance therapeutic efficacy [4,5].Polymeric micellar na-noparticles can be thermodynamically stable,and the hydrophil-ic shell ensures its stable dispersion in aqueous solution through a steric stabilization effect,which facilitates its long term blood circulation following intravenous injection [6].These advan-tages make polymer micellar nanoparticles promising for hy-drophobic drug delivery.Challenge is remained in development of cellular specific polymeric micellar system for targeted drug delivery.Biofunc-tional molecules or ligands are expected to be conjugated to micelle surface for specific cell binding and internalization.In this regard,functionable groups at the end of hydrophilic polymer segments are generally required for bioconjugation.Most reported functionalized polymeric micellar systems are based on block copolymers of hydrophobic aliphatic polyester andAvailable online at Journal of Controlled Release 128(2008)32–40/locate/jconrelCorresponding author.Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences,University of Science and Technology of China,Hefei,Anhui 230027,PR China.Tel.:+865513600335;fax:+865513600402.E-mail address:jwang699@ (J.Wang).1Contribute equally to this work.0168-3659/$-see front matter ©2008Elsevier B.V .All rights reserved.doi:10.1016/j.jconrel.2008.01.021functionalized hydrophilic poly(ethylene glycol).For example, Kataoka et al.reported sugar and small peptidyl ligands modified polymer micelles and reactive polymer micelles based on an aldehyde-ended poly(ethylene glycol)/poly(lactide)block copo-lymer[7,8].Langer et ed carboxy-terminated poly(D,L-lactide-co-glycolide)-block–poly(ethylene glycol)to fabricate micellar nanoparticles for surface conjugation of prostate specific membrane antigen binding aptamer[9–11].Liang et al.reported polymer micelles of poly(γ-benzyl L-glutamate)/poly(ethylene glycol)diblock copolymer end capped with galactose moiety for liver targeted drug delivery[12].Instead of conjugation to the end of hydrophilic polymer segments,biofunctional molecules or ligands have also been conjugated to the side groups of hydrophilic block,such as galactosamine-conjugated micelles based on poly(γ-glutamic acid)(γ-PGA)and poly(lactide)(PLA) block copolymer[13–15].In the past few years,we have developed biocompatible po-lyphosphoesters for drug/gene delivery and tissue engineering, taking their advantages of biodegradability and structural flex-ibility[16–18].We have reported two convenient methods to synthesize structurally and compositionally defined block copolymer of poly(ɛ-caprolactone)(PCL)and polyphosphoester. One method was sequential polymerization ofɛ-caprolactone and cyclic phosphoester monomer with trimer of aluminum isoprop-oxide as the initiator[19].The other method was to use PCL macroinitiator to initiate cyclic phosphoester monomer polymer-ization with stannous octoate as the catalyst[20].Through these two methods,polyphosphoesters with hydroxyl end groups can be conveniently synthesized.On the other hand,we have recently demonstrated in aqueous solution triblock copolymers of PCL and poly(ethyl ethylene phosphate)(PEEP)formed micellar nanoparticles with hydrophobic PCL core and hydrophilic PEEP shell[17].As compared with the well-known poly(ethylene glycol),hydrophilic polyphosphoesters may hold interesting properties for drug delivery system design since polypho-sphoesters are degradable and more structurally flexible for physicochemical property adjustment.The aim of this study is to develop reactive micelles for surface ligands conjugation using block copolymer of PCL and polyphosphoesters and study its potential for cellular specific drug delivery.We synthesized diblock copolymer of PCL and PEEP and further activated the hydroxyl end groups of PEEP by reaction with N,N′-carbonyldii-midazole.In aqueous solution,the activated diblock copolymer assembled into micellar nanoparticles with surface ready to react with amine(s).D-Galactosamine was then conjugated to the surface of these micellar nanoparticles.The potential of such system for targeted anticancer drug delivery to HepG2cells was studied by examining asialoglycoprotein receptor(ASGP-R) mediated cell binding and internalization ability and bioactivity of paclitaxel-loaded micelles.2.Materials and methods2.1.Materials2-Ethoxy-2-oxo-1,3,2-dioxaphospholane(EEP)was synthe-sized and purified as previously reported[20].Tetrahydrofuran (THF)was refluxed over potassium–sodium alloy under N2at-mosphere and distilled out just before use.PCL macroinitiatorbearing one hydroxyl end group per polymer chain(PCL67–OH) was synthesized by ring-opening polymerization ofɛ-caprolac-tone in THF using aluminum isopropoxide as the initiator[19].The polymerization degree of the PCL macroinitiator was67,which was calculated based on the integration ratio of the tripletresonance at4.03ppm(2H)and the singlet resonance at3.66ppm(2H)from its1H NMR.The molecular-weight distribution ofPCL67–OH was1.16which was determined by gel permeation chromatography(GPC)as described below.Stannous octoate(Sn (Oct)2)was purified according to a method described in literature [20].D-Galactosamine hydrochloride(98%),D-glucosamine hydrochloride(99%),N,N′-carbonyldiimidazole(CDI,98%), and paclitaxel were obtained from Sigma-Aldrich Co.All other solvents were of reagent grade and used as received.Dialysis membrane tubing Spectra/Por®Float-A-Lyzer(MWCO25,000) was obtained from Spectrum Laboratories,Inc.2.2.Syntheses and characterization of polymers2.2.1.Synthesis of block copolymer(PCL–PEEP)Block copolymer PCL–PEEP was obtained by ring-opening polymerization of EEP using PCL67–OH as the initiator and Sn (Oct)2as the catalyst.Briefly,to a solution of EEP(7.60g, 50.0mmol)and PCL67–OH(7.64g,1.0mmol)in THF at35°C was added Sn(Oct)2(0.41g,1.0mmol).After3h reaction,the mixture was concentrated and the polymer was precipitated in cold ethyl ether twice.The obtained block copolymer PCL–PEEP was dried under vacuum to a constant weight at room temperature.The yield was approximately75%.The degree of polymerization(DP)of EEP was calculated based on the integration ratio of resonance at 4.18and4.26ppm(6H),assigned to methylene protons of PEEP block,to resonance at2.35ppm(2H),assigned to the methylene protons of PCL block(Fig.1A).Based on this calculation,the DP of EEP was36,with respect to72%EEP conversion.The mol-ecular-weight distribution was1.40,determined by gel perme-ation chromatography.This copolymer was further denoted as PCL67–PEEP36.Fig.1.1H NMR spectra of PCL67–PEEP36(A),PCL67–PEEP36–CDI(B)and glucose-conjugated block copolymer(C).33Y.-C.Wang et al./Journal of Controlled Release128(2008)32–402.2.2.Synthesis of CDI activated block copolymer(PCL67––PEEP36––CDI)Block copolymer PCL67–PEEP36(1.0g)and CDI(65mg,5.0 equiv mol of hydroxyl groups)were dissolved in10mL of anhydrous THF.The solution was stirred at room temperature for 12h,and then concentrated.The polymer was precipitated into anhydrous ethyl ether.The activated block copolymer PCL67–PEEP36–CDI was obtained by filtration and then dried under vacuum.The yield was approximately90%.2.2.3.Characterization and measurementsBruker A V300NMR spectrometer(300MHz)was used for1H NMR spectrum analyses to determine the structure and composi-tion of block copolymers.Deuterated chloroform containing 0.03v/v%tetramethylsilane was used as the solvent for NMR measurements.Molecular weights and molecular-weight distri-butions were determined by gel permeation chromatography measurements on a Waters system,equipped with a Waters1515 HPLC solvent pump,a Waters2414refractive index detector,and four Waters Styragel columns(HR4,HR2,HR1,HR0.5,effective molecular-weight range5000–500,000,500–20,000,100–5000, 0–1000respectively).HPLC grade chloroform was purchased from J.T.Baker and used as the eluent at40°C,delivered at a flow rate of1.0mL min−1.Monodispersed polystyrene standards obtained from Waters Co.with a molecular-weight range1310–5.51×104were used to generate the calibration curve.2.3.Preparation and characterization of polymer micelles2.3.1.Preparation of micellesMicelles were prepared by a dialysis method.PCL67–PEEP36–CDI(50mg)was dissolved in5mL of THF.To this solution was added dropwise100mL of Milli-Q water(Millipore Milli-Q Synthesis,18.2MΩ)under gentle stirring.After standing at room temperature for3h,THF was removed by dialysis against Milli-Q water for24h.2.3.2.Conjugation of D-galactosamine and D-glucosamine to micelle surfaceD-Galactosamine or D-glucosamine was conjugated to micelle surface via reaction with micelles as described above.D-Galac-tosamine or D-glucosamine was dissolved into micelles at pH9.0. After24h reaction at room temperature,micelles were dialyzed against Milli-Q water for24h to remove free D-galactosamine or D-glucosamine.The contents of D-galactosamine and D-glucosa-mine conjugated to micelles were determined by the colorimetric Morgan Elson assay[21].2.3.3.Characterization of polymer micellesTo confirm the surface functionality of micelles,micelles in aqueous solution was lyophilized and dissolved in CDCl3.1H NMR spectrum was recorded using Bruker A V300NMR spectrometer(300MHz).The methods for critical micelle con-centration(CMC)determination,transmission electron micro-scopy(TEM)observation,and particle size and zeta potential measurements were described in detail in the supplementary information.2.4.Cell binding and internalization studies2.4.1.Preparation of rhodamine123-loaded micellesRhodamine123-loaded micelles were prepared in a similar method as described in Section 2.3.1.PCL67–PEEP36–CDI (10mg)and rhodamine123(0.1mg)were dissolved in THF (5mL),and10mL of Milli-Q water was added dropwise to this solution under gentle stirring.THF was removed by dialysis against water for24h.Conjugation of D-galactosamine or D-glu-cosamine to micelle surface was done as described in Section 2.3.2.Micelle with D-glucosamine or D-galactosamine conjuga-tion was denoted as NP-Glu or NP-Gal,respectively.The control micelles(NP)without any saccharide moiety was made using PCL67–PEEP36in a similar method.2.4.2.Binding of micelles to HepG2cellsHepG2cells(150,000cells per well)in24-well plates were precultured with100μL of rhodamine123-loaded NP,NP-Glu or NP-Gal in phosphate-buffered saline(PBS,1mg mL−1)at4°C for 1h.Cells were washed with ice-cold PBS and further cultured with1mL of complete DMEM(Dulbecco's Modified Eagle's Medium,containing10%Hyclone fetal bovine serum,50units mL−1penicillin and50units mL−1streptomycin)at37°C and5% CO2atmosphere.At different culture intervals,cells were se-parately harvested by trypsinization,washed with PBS and resus-pended in200μL of PBS for flow cytometric analysis using a Becton Dickinson FACSCalibur flow cytometer.2.4.3.Cellular uptake of micelles by HepG2cellsRhodamine123-loaded micelles(100μL,1mg mL−1in PBS)were incubated with150,000HepG2cells in1mL of complete DMEM culture medium.For the competing inhibition study,D-galactosamine was added to reach the final concentra-tion of20mM.After incubation at37°C for4h,cells were trypsinized,washed with PBS twice,resuspended in200μL of PBS and subjected to flow cytometric analysis.For microscopic observation,HepG2cells(5×104)were seeded on coverslip in a24-well tissue culture plate until they were totally adherent.100μL of Rhodamine123-loaded NP or NP-Gal(1mg mL−1in PBS)were added to distinct wells and incubated at37°C for2h in1mL of complete DMEM culture medium.The cells were washed and fixed with4%formalde-hyde and the slides were mounted and observed with a Zeiss LSM510Laser Confocal Scanning Microscope imaging system with an upright confocal microscope and a40×objective.2.5.Drug loading and activity analyses2.5.1.Preparation of paclitaxel-loaded micellesPaclitaxel was loaded into micelles by the dialysis method.In a typical procedure,the block copolymer(10mg)was dissolved in 1.0mL of THF,and to this solution was subsequently added paclitaxel dissolved in DMSO at various weight ratios to block copolymer(paclitaxel/polymer=0.05–0.1).Milli-Q water was then added dropwise to this solution.The mixture was stirred at room temperature for3h and filtered through0.45μm Millipore membrane filter.The solution was dialyzed for24h and freeze-34Y.-C.Wang et al./Journal of Controlled Release128(2008)32–40dried.Paclitaxel-loaded NP-Gal is further denoted as NP-Gal-PTX,while the control NP-PTX was made using PCL67–PEEP36 without D-galactosamine conjugation in a similar method.After dissolving paclitaxel-loaded micelles with acetonitrile–water(50:50,v/v),the loading amount of paclitaxel was deter-mined by HPLC analysis.HPLC analysis was performed on a Waters HPLC system consisting of Waters1525binary pump, Waters24872-channel UV–vis detector,1500column heater and a Symmetry C18column.HPLC grade acetonitrile–water (50:50,v/v)was used as the mobile phase at30°C with a flow rate of1.0mL min−1.UV–vis Detector was set at227nm and linked to Breeze software for data analysis.Linear calibration curves for concentrations in the range of0.098–100μg/mL were constructed using the peak areas by linear regression analysis.The regres-sion equation was calculated as y=42204x+8287.8(R2= 0.9996).The concentrations of paclitaxel were determined by comparing the peak area with the stand curve.The drug loading content(DLC)and drug loading efficiency(DLE)were calculated by the following equations:DLC¼weight of PTX in micellesweight of PTX loaded micellesÂ100kDLE¼weight of PTX in micellesweight of PTX used for encapsulationÂ100k2.5.2.In vitro paclitaxel release from micellesIn vitro release profiles of paclitaxel from micelles were investigated in phosphate-buffered saline(PBS,0.02mol L−1,pH 7.4)using a dialysis-bag diffusion technique.Micelles(1.5mL) were introduced into a dialysis membrane tubing and incubated in 25mL of buffer at37°C with stirring.At predetermined intervals, buffer were drawn and replaced with an equal volume of fresh medium.The concentration of paclitaxel in the solution was measured by HPLC.2.5.3.Viability of HepG2cells treated with paclitaxel-loaded micellesThe cytotoxicity of NP-Gal-PTX or NP-PTX against HepG2 cells was evaluated in vitro by MTT assay,using paclitaxel dissolved in DMSO as the control(the final concentration of DMSO in medium was1%v/v).HepG2cells were seeded in96-well plates at10,000cells per well in100μL of complete DMEM medium and incubated at37°C in5%CO2atmosphere for24h. The culture medium was replaced with100μL of fresh medium containing paclitaxel-loaded micelles.Various PTX concentra-tions were achieved by adding dilution of the micelle formulation with4.0%of drug loading content.Cells were further incubated for72h,followed by addition of25μL of MTT stock solution(5mg mL−1in PBS)to achieve a final con-centration of1mg mL−1.After incubation for an additional2h, 100μL of the extraction buffer(20%SDS in50%DMF,pH4.7, prepared at37°C)was added to the wells and incubated over-night at37°C.The absorbance of the solution was measured at 570nm using a Bio-Rad680microplate reader and cell viability was normalized to that of HepG2cells cultured in the culture medium without paclitaxel.2.5.4.Cell cycle analyses of HepG2cells treated with paclitaxel-loaded micellesHepG2cells cultured in24-well plates were treated for24hwith paclitaxel in DMSO,NP-PTX or NP-Gal-PTX at threedifferent paclitaxel doses(0.075,0.3,and1.2μM).For cellstreated with paclitaxel in DMSO,the final concentration ofDMSO in medium was kept at1%(v/v).The cells were tryp-sinized,washed with PBS,fixed with70%ethanol and cen-trifuged.The cell pellet was suspended with PBS and treatedwith200μL of propidium iodide(PI)staining solution(0.1%Triton X-100,0.2mg mL−1DNase-free RNase A and20μgmL−1PI)for15min at37°C.The fluorescence was measuredusing flow cytometer and cell cycle was analyzed usingWinMDI2.9software.3.Results and discussion3.1.Synthesis and characterization of block copolymersWe have previously reported polyphosphoesters with linearmolecular structure can be synthesized through ring-openingpolymerization of EEP in THF under co-initiation of dodecanoland Sn(Oct)2[20].Instead of dodecanol,we have also used PCLdiol as the initiator to synthesize triblock copolymer of PCL andPEEP[17].In this study,mono hydroxyl-terminated poly(ɛ-caprolactone)PCL67–OH was used as macroinitiator for EEP polymerization to obtain a diblock copolymer(Scheme1).Thefeeding molar ratio of PCL67–OH to EEP was1:50,while the reaction time was limited to3h since extension of reaction time will likely lead to chain exchange side reaction though EEP conversion can be increased[20].Such copolymer chains contain functional hydroxyl groupsat the end of PEEP segments,which was demonstrated by thepresence of resonance appeared at3.82ppm,assigned to me-thylene protons conjoint to hydroxyl end groups of polypho-sphoester block(Fig.1A)as reported by us previously[17,19].These hydroxyl end groups can be conveniently modified forbiofunctional molecules conjugation.As depicted in Scheme1,in this study,coupling reagent CDI was used to activatetheScheme1.Schematic illustration of syntheses of block copolymer and surface functionalized micelles.35Y.-C.Wang et al./Journal of Controlled Release128(2008)32–40hydroxyl groups and generate the carbonylimidazole derivative PCL67–PEEP36–CDI,while imidazole groups are known to be easily substituted under the attack of nucleophiles such as amines.1H NMR analysis of PCL67–PEEP36–CDI demon-strated the successful conversion of hydroxyl groups to car-bonylimidazole moieties.As shown in Fig.1B,no signal at 3.82ppm was further found in1H NMR spectrum of PCL67–PEEP36–CDI.Instead,newly appeared resonance at4.62ppm should be assigned to protons of methylene groups conjoined to the end carbonyl group of PCL67–PEEP36–CDI.In addition,the presence of resonances at7.21,7.45and8.20ppm,should be assigned to protons of imidazole residues,demonstrating the successful activation of hydroxyl groups of PEEP blocks.3.2.Micelle preparation and characterizationPCL67–PEEP36–CDI is amphiphilic and in aqueous medium it self-assembled to form micellar structure.The spherical morphology of micelles was demonstrated by TEM examina-tion,shown in the supplementary information(Fig.S1).The CMC value of PCL67–PEEP36–CDI,which describes the physical properties of the micelles relating to its thermodynamic stability,was determined by the method based on partition of pyrene probe in hydrophobic core against aqueous environment [22].The intensity ratio of the bands at339.0and335.5nm (I339.0/I335.5)as a function of the logarithm of the copolymer concentration was given in supplementary information(Fig.S2). The CMC value of PCL67–PEEP36–CDI,which was8.9×10−4mg mL−1,was taken at the intersection of the tangents to the horizontal line of intensity ratio with relatively constant values and the diagonal line with rapid increased intensity ratio.3.3.Conjugation of D-galactosamine and D-glucosamine to micelle surfaceD-Galactosamine and D-glucosamine were conjugated to mi-celle surface via substitution of imidazole by amino groups.To demonstrate the successful conjugation,micelle in aqueous solution was lyophilized after conjugation and the polymer was extracted into CDCl3for1H NMR analyses.As shown in Fig.1C, resonances corresponding to imidazole residue protons disap-peared.Instead,newly appeared peaks at3.3–3.8,5.01and 6.02ppm were due to the presence of glucosyl protons and its anomeric protons(a and a'),indicating the complete substitution of imidazole by glucosyl residues.The contents of D-galactosa-mine and D-glucosamine conjugated to micelles determined by the colorimetric Morgan Elson assay[21]were59.6±8.2nmol mg−1and65.1±10.2nmol mg−1,corresponding to78.2±10.7mol%and85.4±13.3mol%of total end groups,respectively. The CMC of sugar-conjugated block copolymer was comparable to PCL67–PEEP36and PCL67–PEEP36–CDI as determined by the same method described above.In addition,average size(about 70nm in diameter)and size distribution of micelles were not significantly affected after sugar conjugation that was measured by dynamic light scattering and given in supplemental informa-tion(Fig.S3A).However,with the conjugation of sugar mo-lecules,the micelles were more negatively charged compared with PCL67–PEEP36–CDI micelles.The average zeta potential value was around−20mV(Fig.S3B),which may promote micelle stabilization due to static repellency between particles.3.4.Cell binding and internalizationThe asialoglycoprotein receptor(ASGP-R)on the surface of hepatoma cells is a recycling endocytotic receptor and re-cognizes galactose-and N-acetylgalactosamine-terminaled gly-coproteins[23].To demonstrate the enhanced binding ability of galactosamine-conjugated micelles(NP-Gal)to HepG2cells, the micelles were loaded with rhodamine123fluorescent dye and incubated with HepG2cells at4°C.Micelles not bound to cell surfaces were washed off after1h incubation,and the cells were further cultured under normal cell culture conditions at 37°C.Because cell internalization of nanoparticles via endocy-tosis is an ATP-dependent process,micelles attached to cell surface should not be internalized by cells at4°C[24].Further incubation of cells with attached nanoparticles on cell membrane at37°C allowed micelle internalization into cells and rhodamine 123release.As shown in Fig.2A,the fluorescent intensity of HepG2cells right after1h treatment with NP-Gal micelles at4°C was slightly higher than those treated with non-modified micelles(NP)or glucosamine-conjugated micelles(NP-Glu), which was also indicated as the relative geometrical mean fluorescence intensity(GMFI)shown as the inset.The fluo-rescent positive cell population was around18%after incubation at4°C with NP-Gal.It is worth noting that high concentration of rhodamine123in micellar core might result influorescenceFig.2.Flow cytometric analyses of binding ability of non-modified micelles (NP,blue),glucosamine-conjugated micelles(NP-Glu,green),and galactosa-mine-conjugated micelles(NP-Gla,red)to HepG2cells.Cells were mixed with micelles at4°C for1h and further incubated at37°C for0(A),75(B),150(C) and180min(D).Blank cells incubated with micelle free medium were used as the control(purple).The relative geometrical mean fluorescence intensity (GMFI)of cells incubated with NP,NP-Glu and NP-Gal are shown as insets. (For interpretation of the references to colour in this figure legend,the reader is referred to the web version of this article.)36Y.-C.Wang et al./Journal of Controlled Release128(2008)32–40quenching therefore fluorescence detected by flow cytometry could be relatively weak.Fig.2B –D shows the results analyzed by flow cytometry when HepG2cells were further incubated at 37°C following the micelle attachments to cell membrane.It is obvious that with elongation of incubation time from 75to 180min,positive cell population (with log mean fluorescence intensity more than 101)increased from 28.9%to 76.6%,while the relative GMFI increased from 1.65to 6.39in the group treated with NP-Gal,indicating more rhodamine 123-loaded micelles attached to HepG2cells at 4°C were internalized and the cargo was released.In contrast,fluorescence of cells treated with NP or NP-Glu was much less pronounced due to their poor attachment to HepG2cells at 4°C.This phenomenon demon-strated that the ligand –receptor recognition between galactosyl residue and ASGP-R mediated the surface binding of micelles to HepG2cells.It is possible that negatively charged surface of micelles resulted in electrostatic repulsion to cells,which in fact is unfavorable to micelle binding to cell surface.Therefore,without receptor mediation,NP-Glu and NP had less chance to reach HepG2cell surface and be internalized into cells.In another experiment,HepG2cells were directly incubated at 37°C with rhodamine 123-loaded micelles.Cellular accumula-tion of rhodamine 123was analyzed and results were shown in Fig.3A –C.Incubation of NP-Gal with HepG2cells at 37°C for 4h resulted in increased cell population with high fluorescence (66.2%with log mean fluorescence intensity more than 102),indicating significant micelle internalization and rhodamine 123release.On the contrast,the percentage of cell population with log mean fluorescence intensity more than 102were less than 7%when cells were incubated with NP or NP-Glu,demonstrating only minimal micelles were taken up by HepG2cells without receptor mediation.In the presence of 20mM galactosamine,the uptake of NP-Gal was significantly inhibited,which was char-acterized by the relative GMFI of HepG2cells incubated with orwithout galactosamine (Fig.3D),suggesting that cellular uptake of NP-Gal was mediated by the asialoglycoprotein receptors.Fig.4showed the differential interference contrast (DIC),fluorescence and merged images of HepG2cells after 2h incubation at 37°C with rhodamine-123loaded micelles with or without galactosamine conjugation.The intensity of fluores-cence observed in HepG2cells incubated with NP-Gal markedly increased when compared with that of HepG2cells incubated with non-modified NP.It further confirmed the preponderance of NP-Gal on cellular uptake due to the interaction between galac-tosyl moieties with ASGP-R of HepG2cells.3.5.Delivery of paclitaxel to HepG2cellsPaclitaxel is a highly hydrophobic anticancer drug that has a poor solubility (approximately 1μg/mL in aqueous solution at pH 7.4)[25,26].Amphiphilic block polymers,which self-assemble to nanoparticles in aqueous solution,have been often employed as the vehicle to load paclitaxel into the hydrophobic core for enhanced delivery efficiency [27].In paclitaxel loadingprocedureFig. 3.Flow cytometric analyses of cellular rhodamine 123fluorescence intensity of HepG2cells incubated with galactosamine-conjugated micelles (NP-Gal),glucosamine-conjugated micelles (NP-Glu)or non-modified micelles (NP)at 37°C for 4h (A –C),and the relative geometrical mean fluorescence intensity (GMFI)of HepG2cells cultured with NP-Gal in the absence (−Gal)or presence (+Gal)of 20mM of galactosamine(D).Fig.4.Differential interference contrast (A),fluorescence (B)and merged (C)images of HepG2cells after 2h incubation with non-modified micelles (NP)or galactosamine-conjugated micelles (NP-Gal)at 37°C.Table 1Drug loading efficiency (DLE)and drug loading content (DLC)of micelles prepared at various feeding weight ratios of paclitaxel to block copolymerFeed weight ratio of polymer to PTX DLE (%)DLC (%)10:144.2 4.4220:157.5 2.8750:177.4 1.55200:192.90.4737Y.-C.Wang et al./Journal of Controlled Release 128(2008)32–40。

分子沉积膜的纳米摩擦特性

Nanofriction properties of molecular deposition films WANG Qiangbin 1,2, GAO Manglai 1, ZHANG Siwei 11. Department of Chemical Engineering, University of Petroleum, Beijing 102200, China;2. Institute of Technical Chemistry Physics, East China University of Science & Technology, Shanghai 200237, ChinaCorrespondence should be addressed to Wang QiangbinAbstract The nanofriction properties of Au substrate and monolayer molecular deposition film and multilayer molecular deposition films on Au substrate and the molecular deposition films modified with alkyl-terminal molecule have been investigated by using an atomic force microscope. It is concluded that (i) the deposition of molecular deposition films on Au substrate and the modification of alkyl-terminal molecule to the molecular deposition films can reduce the frictional force; (ii) the molecular deposition films with the same terminal exhibit similar nanofriction properties, which has nothing to do with the molecular chain-length and the layer number; (iii) the unstable nanofriction properties of molecular deposition films are contributed to the active terminal of the molecular deposition film, which can be eliminated by decorating the active molecular deposition film with alkyl-terminal molecule, moreover, the decoration of alkyl-terminal molecule can lower the frictional force conspicuously; (iv) the relative humidity affects the frictional force; the higher the RH, the lower the frictional force.Keywords: Au substrate, molecular deposition (MD) film atomic force microscope (AFM) nanofriction nanolubrication.Nanotribology is a new science and technology to experimentally and theoretically investigate interfacial processes including adhesion, contact formation, friction, wear, lubrication,nanoindentation, fracture and machining[1] on the atomic and molecular scales to the microscale.Presently, the study of the organic ultrathin film focuses on the Langmuir-Blodgett films and selfassembled films. The molecular deposition (MD) film[2 4] is prepared through electrostatic attraction between opposite charges from cationic and anionic compounds. It is active due to the charge on its surface. A multilayer film can be built through alternating deposition of a bipolar cationic compound and a bipolar anionic compound. However, the tribological performance of MD film has scarcely been studied until now. In reality an understanding of nanofriction properties is crucial for developing new nanolubrication technology.In this paper, the nanofriction features of different MD films on the Au substrate are systematically studied, and the effects of load, scan rate, molecular terminal and relative humidity on the nanofriction properties are discussed.1 Preparation of samples1.1 The ionization of Au substrateDip a clear Au substrate into an ethanol solution saturated with3-mercapto-1- propanesulfonic acid for 12 h, clean it up with de-ionized water and dry it in a vacuum-desiccator.Finally,the anionic Au substrate was obtained.1.2 The development of MD filmAfter immersing the anionic Au substrate into an ethanol solution saturated with 4,4-dipyridyl dihydrochloride for 12 h, the monolayer MD film was gained. By putting it in a 1mg·10mL copper ( II) phthalocyaninetetrasulfonic acid tetrasodium salt solution (pH=5-6) for 12 h the bilayer MD film was formed. Repeat the above process. Then the trilayer and tetralayer MD film were obtained. The monolayer MD film and the trilayer MD film have the same terminal (-NH+), and the bilayer MD film and the tetralayer MD film have the same terminal(-SO3-). The preparation of the MD film is shown in fig.1.Fig.1. Preparation of a multilayer MD film and the alkyl-termination process.1.3 The modification of the MD film with alkyl-terminal moleculePutting the monolayer MD film and trilayer MD film into a 1.2×10-4 mol·L-1 dodecyl-phenylsulfonate sodium salt solution for 12 h, we gained the alkyl-terminated monolayer and trilayer MD films. In the same way, by dipping the bilayer film and tetralayer MD film into a 1.0×10-4 mol·L-1 catyltrimethylammonium bromide solution for 12 h, the alkyl-terminated bilayerand tetralayer MD films were obtained. All the four alkyl-terminated MD films have the sameterminal (-CH3).1.4 Experimental equipment and methods and reagents (see ref. [5]).2 Results and discussions2.1 Effects of the load on the frictional forceThe experiments of the above five kinds of surfaces with the constant scan rate of 20 mm s-1and 75% RH (relative humidity) indicated that frictional forces produced on various surfaces had different effects on the load.Fig.2. Frictional force vs load on different surfaces. 1, Clean Au substrate; 2, monolayer MD film;3, bilayer MD film; 4,trilayer MD film; 5, tetralayer MD film.Fig. 2 shows that for the Au substrate, the frictional force increased conspicuously with the increase in the load. The frictional forces of the monolayer and trilayer MD films first increased and then decreased with the increase in load. As for the bilayer and tetralayer MD films, the frictional forces were proportional to the load.The experimental results showed that the deposition of MD film on Au substrate had certain lubrication effects. Especially for the trilayer MD film, the frictional force was the lowest. It was noticeable that the MD films with the same terminal had the same nanofriction properties during the experiment. The nanofriction property of monolayer MD film was the same as that of the trilayer MD film, and so were the bilayer and tetralyer MD films. This phenomenon could be explained as follows. Firstly, the interlayer attraction of the MD film is strong enough to ensure that the energy be dissipated only by the vibration and the rotation of the terminal of the MD film during the interaction of the AFM probe and the samples. Secondly, according to JKR theory[5], the adhesion is proportional to the square root of the radius of the probe tip. Moreover,based on the experimental measurement, the adhesion of MD films on Au substrate is rather low.Therefore, it can be deduced that the contact between the probe tip and the sample surface is in atomic level and the nanofriction properties of the samples are only related to the kind of probe tip and the structure of the molecular terminal on the sample surface, but have nothing to do with the chain-length and the structure of the molecules and the layer number of the films. The fact that the nanofriction property of monolayer MD film increases first and then decreases with the load increasing, which is similar to the nanofriction properties of the monolayerL-B film and the metal under the condition of low load, has not been given any reasonable explanation so far[6].2.2 Effects of the scan rate on the frictional forceThrough the experiments on the five surfaces at different scan rates and the relative humidity(RH) of 75% under 25N load, it has been found that the effects of the scan rate on the frictional force were various for different samples (fig.3).Fig.3. Frictional force vs scan rate for different surfaces. 1,Clean Au substrate; 2, monolayer MD film; 3, bilayer MD film; 4, trilayer MD film; 5, tetralayer MD film.Fig. 3 shows that for the clean Au substrate,the frictional force is much larger than those of the other four kinds of sample, and increases slightly with the increase in scan rate. The frictional force of monolayer MD film decreases as the scan rate increases. In contrast, the frictional forces of the bilayer and trilayer and tetralayer MD films increase with the increase in the scan rate. Moreover, all the Au substrates deposited with MD film have a lower frictional force than the clean Au substrate at different scan rates, and the frictional force of the trilayer MD film is the lowest.The slight changes in the frictional force with scan rate of the clean Au substrate might beaccounted for by its stable surface characteristics during the scanning process under the light loading condition. The frictional forces of the four kinds of MD films decreased as the scan rate was increased during the scanning process due to the characteristics of the layer-structure of the MD film’s “liquid crystal” stat e[7].2.3 Effects of the modification of alkyl molecule on the nanofriction properties of MD filmThe MD films were modified with the alkyl-terminal molecules in the experimentand their nanofriction properties were investigated under the same experimental condition by using AFM. The experimental results showed that there are noticeable differences in the ratio of frictional force to the load and scan between the modified and unmodified MD films as shown in figs.4 and5.Fig.4. Frictional force vs. load for alkyl-terminated MD films.1, Alkyl-terminated monolayer MD film; 2, alkyl-terminatedbilayer MD film; 3, alkyl-terminated trilayer MD film;4, alkylterminated tetralayer MD film.Fig. 5. Frictional force vs scan rate for alkyl-terminated MD films 1, alkyl-terminated monolayer MD film; 2, alkylterminatedbilayer MD film; 3, alkyl-terminated trilayer MD film,4, alkyl-terminated tetralayer MD film.Comparing figs. 4 and 5 with figs. 2 and 3 respectively, we observe that the frictional forces of the MD films are conspicuously lowered after being decorated with alkyl-terminal molecule,and the frictional forces are proportional to the increase in the load and the scan rate. The decrease of frictional force could be attributed to the “molecular brush” effects[8] of the alkylterminal molecule decorated on the MD film surface. The proportionality of the frictional forces to the load and scan rate could be ascribed to the stable surfaces formed after decoration with the alkyl-terminal molecule.It is of interest to note that all the samples with the same terminal (-CH3) after being decorated with alkyl-terminal molecule have the same nanofriction properties.This result further proves the conclusion that the characteristics of nanofriction were mainly determined by the probe tip and the terminal of the sample surface molecule. The unstability of the nanofriction properties of the MD films can be attributed to the charge of the surface of the MD film. It was the “electrostatic force”[9, 11] between the probe tip and the active terminal of the MD film that made the nanofriction behavior unstable.2.4 Effects of relative humidity on the nanofriction properties of MD filmThe effect of relative humidity (RH) on the nanofriction properties of the MD film was studied. The result is shown in fig.6.As humidity increases, the condensed water is increasing and meniscus bridges are formed on the sample surface. Apparently, the frictional forces at the probe tip and MD film interfaces are directly related to the amount of water adsorbed on the surface.Fig.6. Frictional force vs load at different RH for monolayer MD film. 1, RH=40%; 2, RH=75%.Under the condition of low and medium humidity, the water film acting as “lubricant”could only be formed at the tips of asperities where the probe tip and the sample surface contacted each other. As the humidity increases,the condensed water increases and water film forms on all the surfaces. The adsorbed water keeps the solid/solid contacting between the probe tip and the surface and reduces theshear-strength at the interface. Therefore, the frictional force decreases with the increasing humidity.3 Conclusions(1) The deposition of molecular deposition films on Au substrate and the modification of alkyl-terminal molecule to the MD films can reduce the frictional force.(2) The molecular deposition films with the same terminal exhibit similar nanofriction properties, which has nothing to do with the molecular chain-length and the layer number.(3) The unstable nanofriction properties of molecular deposition films are attributed to the active terminal of the molecular deposition film, which can be eliminated by decorating the active molecular deposition film with alkyl-terminal molecule;moreover, the decoration of alkylterminal molecule can lower the frictional force conspicuously.(4) The relative humidity can affect the frictional force: the higher RH, the lower the frictional force.Acknowledgements This work was supported by the National Natural Science Foundation of China (Grant No.59735110). The authors thank Associate Profs. Wang Deguo for his helpful discussions and Lin Li for his help in the experiment.References[1]. Bhushan, B., Jacob, N., Landman, U., Nanotribology: friction, wear and lubrication at the atomic scale, Nature, 1995,374(13): 607.[2]. Gao Manglai, Kong Xiangxing, Sheng Jiacong, et al., Preparation and characterization of functional ultrathin orderedmolecular deposited film, Chemical Journal of Chinese Universities (in Chinese), 1993, 14(8): 1182.[3]. Gao, M. L., Kong, X. X., Zhang, X. et al., Bulid-up of polymeric molecular deposition films bearing mesogenic groups,Thin Solid Films, 1994, 244: 815.[4]. Gao Manglai, Zhang Xi, Shen Jiacong, et al., The molecular deposition film of CuTsPc and TPPS4, Science in China (inChinese), Ser. B, 1995, 25(1): 29.[5]. Wang Qiangbin, Gao Manglai, Zhang Siwei, Study on nanofriction properties of molecular deposition (MD) films on Ausubstrate by atomic force microscopy, Progress in Natural Science, 1999, 9: 10.[6]. Schwarz, U. D., Zwörner, O., Köster, P. et al., Quantitative analysis of the frictional properties of solid materials at lowloads. . Carbon compounds, Physical Review B, 1997, 56(11): 6987. [7]. Zhang Jun, Xue Qunji, LANGMIUR-BLODGETT film and its tribology behaviors, Tribology (in Chinese), 1992, 12(2):97.[8]. Shen Jiacong, Zhang Xi, Sun Yipeng, The molecular deposition film, Progress in Natureal Science (in Chinese), 1997,7(1): 1.[9]. Klein, J., Kumacheva, E., Mahalu, D. et al., Reduction of frictional forces between solid surfaces bearing polymer brushes,Nature, 1994, 370(25): 634.[10]. Bennewitz, R., Reichling, M., Mattias, E., Force micriscopy of cleaved andelectron-irradiated CaF2(111) surfaces in ultrahighvacuum, Surface Science, 1997, 387: 69. [11]. Kai, H., Allen, J. B., Use of atomic force microscopy for the study of surface acid-base properties of carboxylic acidterminated self-assembled monolayers, Langmuir, 1997, 13: 5114.。

苯丙胺类滥用药物简述

苯丙胺类滥用药物简述作者：许荣富，姚付军，张茜， Xu Rongfu， Yao Fujun， Zhang Qian作者单位：首都师范大学化学系,北京,100037刊名：北京教育学院学报(自然科学版)英文刊名：JOURNAL OF BEIJING INSTITUTE OF EDUCATION(NATURAL SCIENCE)年，卷(期)：2007,2(3)1.Forsling M L;Falion J K;hah D The effect of 3,4-Methylenedloxymethamphetamine (MDMA,"ecstasy") and its metabolites on neurohypophysial hormone release from the isolated rat hypothalamus[外文期刊] 2002(03)2.郭菘;杜万君;张大明甲基苯丙胺类混合物-摇头丸滥用方式及其对精神活动的影响[期刊论文]-中国药物依赖性杂志 2000(02)3.Cheng S;Nolte H;Otton S V Simultaneous gas chromatographic determination ofmethamphetamine,amphetamine and their phydroxylated metabolites in plasma and urine[外文期刊] 19974.李金苯丙胺类物质及其检测[期刊论文]-中国药物依赖性杂志 2003(01)5.Gianpiero Boatto;Maria Virginia Faedda;Amedeo Pau Determination of amphetamines in human whole blood by capillary electrophoresis with photodiode array detection[外文期刊] 2002(6)6.An-Shu liau;Ju-Tsungg Liu;Li-Chan Lin Optimization of a simple method for the chiral separation of methamphetamine and related compounds in clandestine tablets and urine samples by β-cyclodextrine modified capillary electrophoresis:a complementary method to GCMS[外文期刊] 2003(1)7.Véronique Piette;Frans Parmentier Analysis of illicit amphetamine seizures by capillary zone electrophoresis 20028.Emmanuel Varesio;Jean-Luc Veuthey Chiral separation of amphetamines by high-performance capillary electrophoresis 19959.Pizarro N;Ortuno J;Farre M Determination of MDMA and its metabolites in blood and urine by gas chromatography-mass spectrometry and analysis of enantiomers by capillary electrophoresis[外文期刊] 2002(03)10.刘伟;沈敏SPME-GC/NPD法快速分析尿液中苯丙胺类化合物[期刊论文]-法医学杂志 1999(02)11.Knut Einar Rasmussen;Stig Pedersen-Bjergaard;Mette Krogh Development of a simple in-vial liquidphase microextraction device for drug analysis compatible with capillary gas chromatography,capillary electrophoresis and high-performance liquid chromatography[外文期刊] 2000 12.Yoo Jeong Heo;Yoon Sung Whang;Moon Kyo In Determination of enantiomeric amphetamines as metabolites of illicit amphetamines and selegiline in urine by capillary electrophoresis using modified β-cyclodextrin[外文期刊] 200013.Satoshi Chinaka;Scishi Tanaka;Nariaki Takayama Simultaneous chiral analysis of methamphetamine and related compounds by capillary electrophoresis[外文期刊] 2000(1)14.沈敏体内滥用药物分析 200315.王玫GDX-403固相萃取分析尿、血中安非他明类毒品 1999(02)17.Peter R Stout;Carl K Horn;Kevin L Klette Rapid simultaneous determination ofamphetamine,methamphetamine,3,4-methylenedioxyamphetemine,3,4-methylenedioxymethamphetarnine in urine by solid-phase extraction and GC-MS:a method optimized for high-volume laboratories 2002(01)18.沈敏;沈保华;向平血、尿中甲基苯丙胺以及代谢物产物苯丙胺的分析研究[期刊论文]-法医学杂志 1997(03)19.Nobuyuki Nagasawa;Mikio Yashiki;Yasumasa Iwasaki Rapid analysis of amphetamines in blood using head space-solid phase microextraction and selected ion monitoring[外文期刊] 199620.Kathryn S;Kalasinsky;Barry Levine Fourier transform infrared spectroscopy techniques for the analysis of drugs of abuse 199321.杨小红;田开珍;王峰高效液相色谱-二极管阵列检测法同时测定临床中毒患者血浆中的甲基苯丙胺及苯丙胺[期刊论文]-色谱 2003(09)22.C Cháfer-Pericás;P Campíns-Faleó;R Herráez-Hemández Application of solid-phase microextraction combined with derivatizafion to the determination of amphetaminesby liquid chromatography 200423.H P Hendrickson;A Milesi-Hallé;E M Laurenzana Development of a liquid chromatography-tandem mass spectrometric method for the determination of methamphetamine and amphetamine using small volumes of rat serum[外文期刊] 2004(2)24.F Sadeghipour;J L Veuthey Sensitive and selective determination of methylenedioxylated amphetamines by high-performance liquid chromatography with fluorimetrie detection[外文期刊]1997(1/2)25.Ming-Ren Fuha;Chiuan-Hung Haunga;Shiang-Ling Lin b Determination of free-form amphetamine in rat brain by ion-pair liquid chromatography-electrospray mass spectrometry with in vivo microdialysis[外文期刊] 200426.Rosa Herraez-Hernandez;Pilar Camp?ns-Falco Derivatization of ephedrine with o-phthaldialdehydefor liquid chromatography after treatment with sodium hypochlorite[外文期刊] 200027.Dinesh Talwar;Ian D Watson;Mike J Stewart Routine analysis of amphetamine class drugs as their naphthaquinone derivative in human urine by high-performance liquid chromtography[外文期刊] 1999 28.Y McAvoy;M D Cole;O Gueniat Analysis of amphetamines by supercritical fluid chromatography,high-Performance liquid chromatography,gas chromatography and capillary zone electrophoresis,apreliminary comparison[外文期刊] 199929.Palar Campims-Falco;Adela Sevillano-Cabeza;Carmen Molins -Legua Amphetamine and methamaphetamine determination in urine by reversed-phase high-performance liquid chromatography with simultaneous sample clean-up and derivatization with 1,2-naphthoquinone 4-sulphonate on solid-phase catridges[外文期刊] 199630.Katja Pihlainen a b;Risto Kostiainen b Effect of the eluent on enantiomer separation ofcontrolled drugs by liquid chromatography-ultraviolet absorbance detection-electrospray ionisation tandem mass spectrometry using vancomycin and native -cyclodextrin chiral stationary phases[外文期刊] 200431.Myung Ho Hyun;Sang Cheol Han;Bruce H Lipshutz Liquid chromatographic resolution of racemic32.Myung Ho Hyun;Jong Sung Jin;Hye Jin Koo Liquid chromatographic resolution of racemic amines and amino alcohols on a chiral stationary phase derived from crown ether[外文期刊] 199933.M Katagi;H Nishioka;K Nakajima Direct high-performance liquid chromatographic and high-performance liquid chromatographic -thermospray -mass spectrometric determination of enantiomers of methamphetamine and its main metabolites amphetamine and p-hydroxymethamphetamine in human urine[外文期刊] 199634.Chandrani Gunaratna;Peter T Kissinger Investigation of stereoselective metabolism of amphetamine in rat liver microsomes by microdialysis and liquid chromatography with precolumn chiral derivatization[外文期刊] 199835.Gianpiero Boatto;Maria Virginia Faedda;Amedeo Pau Determination of amphetamines in human whole blood by capillary electrophoresis with photodiode array detection[外文期刊] 2002(6)36.F P Smith;S Turrina;V Equisetto Complementary use of capillary zone electrophoresis and micellar electrokinetic capillary chromatography for mutual confirmation of results in forensic drug analysis [外文期刊] 1996(1/2)37.Tuulia Hy?tyl?inen;Heli Sirén;Marja -Liisa Riekkola Determination of morphine analogues,caffeine and amphetamine in biological fluids by capillary electrophoresis with the marker technique[外文期刊] 1996(1/2)38.Ulli Backofen;Frand-Michael Matysik;Werner Hoffmann Analysis of illicit drugs by nonaqueous capillary electrophoresis and electrochemical detection 200039.V Craige Trenerry;James Robertson;Robert J Wells Analysis of illicit amphetamine seizures by capillary electrophoresis[外文期刊] 1995(1)urent Geiser;Samir Cherkaoui;Jean -Luc Veuthey Simultaneous analysis of some amphetamine derivatives in urine by uonaqueous capillary electrophoresis coupled to electrospray ionization mass spectrometry[外文期刊] 200041.Ulli Backofen;Frand-Michael Matysik;Werner Hoffmann Analysis of illicit drugs by nonaqueous capillary electrophoresis and electrochemical detection 200042.Jeongeun Choi;Choonmi Kim;Myung Ja Choi Immunological analysis of methamphetamine antibody andits use for the detection of mehtamphetamine by capillary electrophoresis with laser-induced fluorescence[外文期刊] 199843.An-Shu Liau;Ju-Tsungg Liu;Li-Chan Lin Optimization of a simple method for the chiral separationof methamphetamine and related compounds in clandestine tablets and urine samples by β-cyclodextrine modified capillary electrophoresis:a complementary method to GCMS[外文期刊] 2003(1) 44.Iio R;Chinaka S;Takayama N Simultaneous chiral analysis of methamphetamine and related compounds by capillary electrophoresis/mass spectrometry using anionic cyclodextrin[外文期刊] 2005(01)45.Juraj Sevcík;Zdenek Stránsky;Benno A Ingelse Capillary electrophoretic enantioseparation of selegiline,methamphetamine and ephedrine using a neutral β-cyclodextrin epichlorhydrin polymer 1996 46.Yoo Jeong Heo;Yoon Sung Whang;Moon Kyo In Determination of enantiomeric amphetamines as。

以光伏晶硅废料构建三维骨架增强环氧树脂的导热性能

研究与开发CHINA SYNTHETIC RESIN AND PLASTICS合成树脂及塑料， 2023， 40（6）： 16以光伏晶硅废料构建三维骨架增强环氧树脂的导热性能姚健（海南大学材料科学与工程学院，海南海口 570228）摘要：以提纯的光伏晶硅废料为原料，添加高导热的片状BN粉末，采用冰模板法与真空浸渗环氧树脂（EP）相结合的方法制备了EP/Si 3N 4-SiC-BN复合材料，并研究了其性能。

结果表明：Si粉氮化反应产生的晶须在Si 3N 4-SiC-BN三维网络骨架中相互接触并分布在垂直定向的孔隙通道内；BN用量为晶硅废料质量的20%时，EP/Si 3N 4-SiC-BN复合材料的热导率最大，为1.08 W/（m ·K ）；随着BN含量的增加，复合材料的抗弯强度降低，BN用量为晶硅废料质量的5%时，抗弯强度最大，为133.6 MPa。

关键词：环氧树脂光伏晶硅废料氮化硅碳化硅氮化硼冰模板法热导率中图分类号： TQ 323.5 文献标志码： B 文章编号： 1002-1396（2023）06-0016-06Thermal conductivity of epoxy resin enhanced by constructing3D framework with photovoltaic crystalline silicon wasteYao Jian（School of Materials Science and Engineering ，Hainan University ，Haikou 570228，China ）Abstract ： The epoxy resin （EP ）/Si 3N 4-SiC-BN composites were prepared by the combination of ice-templating and vacuum impregnated EP，using purified photovoltaic silicon waste as raw material and adding high thermal conductivity flaky BN powder. The results showed that the crystal whiskers produced by the nitriding of silicon powder were interlinked in the Si 3N 4-SiC-BN skeletons and distributed in vertically orientedpore channels. The maximum thermal conductivity of 1.08 W/（m ·K ） was obtained for the EP/Si 3N 4-SiC-BN composites at the high 20% BN addition. The flexural strength of the composites decreased with the increase ofBN addition and the maximum flexural strength was 133.6 MPa at 5% BN addition.Keywords ： epoxy resin； photovoltaic silicon waste； silicon nitride； silicon carbide； boron nitride； ice-templating； thermal conductivityDOI：10.19825/j.issn.1002-1396.2023.06.04收稿日期： 2023-05-27；修回日期： 2023-08-26。

Colloids and Surfaces A

Colloids and Surfaces A:Physicochem.Eng.Aspects 361 (2010) 180–186Contents lists available at ScienceDirectColloids and Surfaces A:Physicochemical andEngineeringAspectsj o u r n a l h o m e p a g e :w w w.e l s e v i e r.c o m /l o c a t e /c o l s u r faSynthesis and characterization of a functionalized graft copolymer of densiﬁed cellulose for the extraction of uranium(VI)from aqueous solutionsT.S.Anirudhan ∗,S.S.SreekumariDepartment of Chemistry,University of Kerala,Kariavattom,Trivandrum 695581,Kerala,Indiaa r t i c l e i n f o Article history:Received 29September 2009Received in revised form 21February 2010Accepted 21March 2010Available online 27 March 2010Keywords:Graft copolymers Densiﬁed cellulose Uranium(VI)Adsorption isotherm Desorptiona b s t r a c tA novel carboxylate functionalized graft copolymer (PGTDC-COOH)based on TiO 2-densiﬁed cel-lulose (TDC)was prepared by grafting poly(methacrylic acid)onto TDC in the presence of N,N -methylenebisacrylamide (MBA)as a cross-linking agent and Mn(IV)–citric acid as an initiator sys-tem.Adsorbent was characterized using FTIR,SEM,XRD,TG-DTG,BET-N 2adsorption measurements,Boehm and potentiometric titrations.The adsorption efﬁciency of PGTDC-COOH for uranium(VI)from aqueous solutions was examined by batch experiments.The optimum pH was found to be 6.0.Kinetic studies show that the uptake was rapid and equilibrium was established in 1h.The sorption process fol-lows the pseudo-second-order kinetic ngmuir analysis showed that the surface of the adsorbent is uniform and homogeneous in respect to sorption and energy.The adsorption equilibrium constant and maximum adsorption capacity were evaluated to be 0.074L/mg and 99.4mg/g,respectively.Utility of the adsorbent was tested by removing U(VI)from simulated nuclear industry wastewater.The possibility of metal recovery from spent adsorbent was investigated using HCl solutions with different concentrations and greater than 96.0%recovery was achieved with 0.1M HCl.© 2010 Elsevier B.V. All rights reserved.1.IntroductionAdsorption of metal ions from a solution to an adsorbent is con-trolled by the surface functional groups of the adsorbent.Cellulosic ﬁbers generally have very few functional groups that are capable of adsorbing metals.Sorption properties can be improved by grafting new functional groups onto the cellulose backbone.Many differ-ent kinds of functionalities have been studied for their potential to remove metal ions from aqueous solutions such as iminoacetic acid [1],Schiff bases [2],amidoxime [3],amine [4],thiosemicar-bazide [5],carboxylic acid [6],phosphoric acid [7]and sulphonic acid [8]groups.In particular,carboxylic acid functional group is important because of the high potential of the carboxylate function-ality for the removal of heavy metal ions from aqueous solutions [9].Cellulose has two distinct regions,the crystalline zone and the amorphous zone [10].Chemical reactions generally do not take place on the crystalline region of cellulose.On the other hand,embedding TiO 2on cellulose should affect the crystalline struc-ture making it more suitable for activation reaction [11].Earlier workers have demonstrated that by using the TiO 2-densiﬁed cellu-lose for the preparation of the adsorbent,it is possible to take the advantage of high porosity,hydrophilicity,chemical modiﬁability,regular spherical shape,particle size,high density and mechani-∗Corresponding author.Tel.:+914712418782.E-mail address:tsani@ (T.S.Anirudhan).cal strength [11].The sorption of metal ions can be enhanced by grafting functional groups onto cellulose-based matrix.The recovery of uranium(VI)from resources such as sea water,industrial wastewater,industrial phosphoric acid and other waste sources is of great concern,due to the increasing needs of this metal for the production of electricity as well as the expected shortage of this metal in the near future.The limited world reserves and their location in developing countries have led to the development of new techniques for the removal and recov-ery of U(VI),particularly from waste streams of nuclear industries.Adsorption is one of the methods commonly used to remove U(VI)ions from aqueous medium with relatively low metal ion concentrations.This work aims at preparing a new carboxylate functionalized graft copolymer through graft polymerization reac-tion of poly(methacrylic acid)onto TiO 2-densiﬁed cellulose in the presence of N,N -methylenebisacrylamide (MBA)as a cross-linker and Mn(IV)/citric acid as an initiator system for the effective removal of U(VI)from aqueous solutions.The adsorption of U(VI)was studied in batch system with respect to the initial pH,contact time,initial concentration,ionic strength,and adsorbent dose.2.Experiment 2.1.MaterialsHigh purity cellulose used for the preparation of cellulose xanthate was purchased from Fluka,Switzerland.All chemicals0927-7757/$–see front matter © 2010 Elsevier B.V. All rights reserved.doi:10.1016/j.colsurfa.2010.03.031T.S.Anirudhan,S.S.Sreekumari/Colloids and Surfaces A:Physicochem.Eng.Aspects361 (2010) 180–186181Scheme1.Preparation of PGTDC-COOH.were analytical grade.U(VI)stock solution was prepared by using UO2(NO3)2·6H2O(Fluka).Methacrylic acid(MA)and MBA from Fluka,Switzerland,were used for graft copolymerization.Titanium dioxide(rutile)obtained from Travancore Titanium Products Ltd. India,was used for densiﬁcation of cellulose.The chemicals such as KMnO4,CS2,and citric acid were of analytical grade supplied by E. Merck,India Ltd.2.2.Preparation of adsorbentCellulose xanthate viscose wasﬁrst prepared by reacting20g of alkali treated cellulose with10mL CS2and then dissolving in 6%NaOH solution.Titanium dioxide densiﬁed cellulose(TDC)was prepared by the method described by Lei et al.[11].For this,rutile and viscose(containing8.0%cellulose)in the weight ratio1.5:10 were dispersed in a solution of200mL chlorobenzene and100mL pump oil in1Lﬂask.The suspension was agitated with a speed of 300rpm at90◦C for1h.The resulting particles wereﬁltered and washed successively with benzene and methanol.The decomposi-tion of cellulose xanthate was completed by immersing particles in a solution of acetic acid and ethanol in the ratio1:2.The TDC thus obtained was washed with water,dried at60◦C and then sieved to −80+230mesh size of particles correspond to an average diameter of0.096mm.Scheme1represents the general procedure adopted for the preparation of poly(methacrylic acid)grafted TDC(PGTDC-COOH) bearing–COOH functional group.Graft polymerization of MA onto TDC was carried out in water using MnO2/citric acid redox system[12].About10g of TDC was immersed in500mL of0.1N aqueous KMnO4solution (solid–liquid ratio1:50)and shaken for30min at room temper-ature to ensure uniform deposition of MnO2all over the sample surface.After impregnation,the sample was washed repeatedly with distilled water and squeezed betweenﬁlter papers.For graft polymerization,the sample-to-liquid ratio1:50was used.The permanganate-treated sample was immersed in a solution contain-ing citric acid(0.4mequiv./L g of TDC).Methacrylic acid(0.5mL/1g of TDC)and MBA(0.1g)were then added with constant stirring under the controlled supply of N2.The contents were heated at 60◦C for1h.The product PGTDC-COOH was washed with methanol and dried at60◦C and then stored in a desiccator until use.The graft yield was calculated by the following equation:Graft yield(%)=w−w0×100(1)where w is the weight of grafted TDC sample and w0is the weight of TDC.Grafting yield was found to be51.57%.2.3.Equipments and methods of characterizationCharacterization of the graft copolymer was compared with the native cellulose.FTIR spectra of the PGTDC-COOH and cellu-lose were recorded on a KBr disk using a Perkin Elmer IR180 spectrophotometer.X-ray diffraction(XRD)analyses were car-ried out with a Rigakku diffractometer using Cu K␣radiation. In order to study the morphological changes during modiﬁca-tion,the samples before and after modiﬁcation were observed under a Scanning Electron Microscope(SEM)model S-2400Hitachi. Thermal stability of the adsorbents was studied with a Metler Toledo Star thermogravimetric analyzer.The surface area was measured by the BET method using a model Q7/S surface area analyzer(Quantasorb,USA).A potentiometric method[13]was used to determine the pH of point of zero charge(pH pzc).The carboxyl content of PGTDC-COOH was determined by neutral-ization of carboxyl groups of the adsorbent with0.1M NaHCO3 solution using a titration method described by Boehm[14].The cation exchange capacity(CEC)of the adsorbent was determined by NaNO3saturation method using a column operation.The pH and density measurements were made using a pH meter(model ␮-362,Systronics,India)and a speciﬁc gravity bottle,respec-tively.A temperature controlled water bath shaker(Labline,India) with temperature variation of±1◦C was used for the equilibrium studies.The concentration of U(VI)in solution was determined using GBC Avanta A5450atomic absorption spectrophotometer (AAS).2.4.Adsorption experimentsThe adsorption of U(VI)from aqueous solutions onto PGTDC-COOH was investigated through batch experiments.A weighed amount of adsorbent(0.1g)was placed in a100mL Erlenmeyer ﬂask containing50mL U(VI)solution.The initial pH of the solution was adjusted to the desired value by adding0.1M HNO3or NaOH. The contents were shaken at200rpm at desired temperature for a predetermined period of time using water bath shaker and then were centrifuged.The concentration of U(VI)in the supernatant was measured using AAS.The adsorption capacity was calculated using the following mass balance equation:q e=(C0−C e)VW(2) where q e is the equilibrium adsorption capacity(mg/g),C0and C e are the initial and equilibrium concentrations of U(VI)in solution (mg/L),respectively.V is the liquid phase volume(L)and W is the amount of the adsorbent(g).Kinetic studies were conducted using four different initial con-centrations(25,50,75and100mg/L)of U(VI)at30◦C.Samples were withdrawn at regular intervals to plot the amount adsorbed versus time.The effects of contact time(0–120min),solution pH (2–8)and adsorbent dose(0.5–5.0g/L)on U(VI)adsorption were studied.The isotherm experiments were performed at30◦C using different concentrations of U(VI)in the range25–500mg/L at pH 6.0.2.5.Desorption studiesDesorption studies were carried out with varying concen-trations of HCl solutions.The sorbent recovered following the adsorption of10mg/L of U(VI)solution was agitated with50mL HCl solution.The sorbent was then removed by centrifugation. The desorbed uranium in the aqueous solution was estimated as previously.182T.S.Anirudhan,S.S.Sreekumari/Colloids and Surfaces A:Physicochem.Eng.Aspects361 (2010) 180–186Fig.1.FTIR spectra of cellulose,PGTDC-COOH and U(V1)adsorbed PGTDC-COOH.3.Results and discussionThe PGTDC-COOH adsorbent was obtained through the grafting of MA onto TDC using MBA as cross-linker and Mn(IV)/citric acid as initiator.TiO2is embedded in the cellulose skeleton to form a composite matrix.The particles not only increased the density of the composite matrix but also act as a looseﬁller to facilitate the activation.The initiator system abstracts hydrogen from the methyl hydroxyl groups of the cellulose to form active sites on the TDC backbone.These active sites interact with monomer to form graft copolymer.Since a cross-linking agent(MBA)present in the system, a polymer network is formed with free–COOH groups at the chain end.The adsorbent was found to be stable in mineral acids and alkalies.3.1.Adsorbent characterizationThe FTIR spectra of cellulose,PGTDC-COOH and the U(VI) adsorbed PGTDC-COOH are shown in Fig.1.Cellulose exhibits a broad absorption band at3344cm−1characteristic of–OH group and a sharp peak at2900cm−1characteristic of C–H stretching from–CH2group.Appearance of an absorption band at1160cm−1 is attributed to the1–4glycosidic linkage of cellulose[15].The IR spectrum of PGTDC-COOH exhibits a broad signal around 3417cm−1representing the overlap of O–H,C–H,N–H and C–O stretching vibrations[16].The peaks at1638and1510cm−1show the presence of amide carbonyl group and aliphatic amide group, respectively,due to cross-linking.These observations indicate the presence of a polymeric chain in PGTDC-COOH.The sharp bands at1690cm−1( C O)and1450cm−1( C–O)show the presence of–COOH group[17].The presence of these adsorption bands in the IR spectrum of the PGTDC-COOH conﬁrms that MA has been successfully grafted on the cellulose backbone.The C–O stretch-ing vibration of–C–OH group in cellulose at1059cm−1shifts to 1021cm−1in PGTDC-COOH due to grafting.In PGTDC-COOH the peak at721cm−1can be attributed to symmetric O–Ti–O stretch-ing and the peak around632cm−1is indicative of the stretching vibration of Ti–O[18].The adsorption of U(VI)onto PGTDC-COOH caused the shifting of certain peaks in PGTDC-COOH and appear-ance of certain characteristic peaks.The bands at3417,1690, 1450and1021cm−1in PGTDC-COOH were shifted to3430,1705,Fig.2.TG and DTG curves of cellulose and PGTDC-COOH.1468and1034cm−1,respectively in the spectrum of U(VI)loaded PGTDC-COOH.The appearance of a peak at930cm−1U(VI)loaded PGTDC-COOH is characteristic of O U O stretching vibration[19]. Literature suggests that in the modiﬁcation of synthetic and natu-ral polymers by grafting,the grafted polymer chains are covalently linked and inter positioned on the cellulosic backbone polymer [20].The increase in weight of the graft polymer,compared to the original weight of TDC,showed that grafting had occurred.The car-boxylic acid group content in the adsorbent and CEC are also in conformity with the grafting of MA onto cellulose backbone.The thermal degradation of cellulose and PGTDC-COOH has been monitored from ambient to800◦C.The comparative thermal decomposition processes occurring in cellulose and the adsorbent were carried out by TG and DTG analyses and are shown in Fig.2. The thermal decomposition of cellulose occurred in two degrada-tion steps:(1)240–360◦C and(2)360–540◦C.In theﬁrst stage of decomposition(T1=344◦C)almost49.5%is lost due to pyrolysis, and in the second stage(T2=514◦C)92.6%of the initial dry weight is due to carbonization.The TG and DTG curves of the adsorbent indi-cate two stage decomposition between280and400◦C(T1=306◦C) where51.1%loss was observed due to the pyrolytic depolymeriza-tion process.The second stage decomposition between400and 560◦C(T2=540◦C)where71.6%of initial dry weight loss was observed leaving behind TiO2residue and char.The initial decom-position temperature(280◦C)and the temperature at50%weight loss(380◦C)of the grafted polymer were higher than those of the ungrafted cellulose(240and360◦C,respectively).The results indi-cate that grafting poly(methacrylic acid)onto cellulose results in an increase in thermal stability.SEM photographs of the cellulose and PGTDC-COOH are shown in Fig.3.The celluloseﬁbers exhibit distinctﬂake and are lump-ish because of the strong intra-molecular hydrogen bonds[21]. The PGTDC-COOH possesses a porous structure due to the incor-poration of polymer chains which hampered the formation of intra-molecular hydrogen bonds.Such a porous structure should signiﬁcantly increase the available surface area of the adsorbent and therefore,increase the adsorption capacity.The grafted side chain through covalent bonding of methacrylic acid seems to form a heterogeneous surface in the graft copolymer showing proof of grafting.The XRD patterns of the cellulose,PGTDC-COOH and U(VI)-adsorbed PGTDC-COOH are shown in Fig.4.Curve(a)reports peaks at16.5◦,22.6◦and33.9◦which constitute the partial crystallineT.S.Anirudhan,S.S.Sreekumari/Colloids and Surfaces A:Physicochem.Eng.Aspects361 (2010) 180–186183Fig.3.Scanning electron micrographs of cellulose and PGTDC-COOH. nature of cellulose like all natural polymers[22].This indicates that cellulose molecules are arranged in ordered lattice in which –OH groups are bonded by strong secondary forces.The diffraction peaks of PGTDC-COOH suggested it to be more crystalline related to the presence of TiO2as denser material for modiﬁcation.The major peak appeared at2Â=27.5◦corresponds to the presence of rutile [23].It can be seen from the curves(b)and(c)that U(VI)loaded PGTDC-COOH retains the XRD patterns of PGTDC-COOH even after loading,with increasing intensity of the peaks at2Â=36.1◦,44.6◦and54.4◦[24].The surface charge density( 0)of the cellulose and PGTDC-COOH was determined by batch potentiometer titration procedure.For titration experiments0.1g of adsorbent was added to50mLFig.4.XRD patterns of cellulose,PGTDC-COOH and U(V1)adsorbedPGTDC-COOH.Fig.5.Surface charge density of cellulose and PGTDC-COOH as a function of pH inaqueous solution of NaNO3.of0.1M NaNO3.The pH of the solutions were carefully adjustedbetween2and8with0.1M HNO3and NaOH solutions,and thensuspensions were shaken in a water bathﬂask shaker at200rpmfor6h.Find out the volumes of alkali and acid required to changethe pH.The values of 0can be calculated using the equation:0=F(C A−C B)+([OH−]−[H+])A(3) where F is the Faraday constant(96485C/g equiv.),C A and C B are theconcentrations of strong acid and base after each addition duringtitration(equiv./L),and[H+]and[OH−]are the equilibrium concen-trations of H+and OH−ions,respectively,bound to the suspensionsurface(equiv./cm2).A plot of 0versus pH is given in Fig.5.Thepoint of intersection of 0with the pH curves gives the pH pzc of5.0and5.6for cellulose and the adsorbent,respectively.The cationexchange capacity(CEC)of cellulose and PGTDC-COOH was foundto be0.69and1.50mequiv./g,respectively.The carboxylic acidgroup content in PGTDC-COOH was found to be1.88mequiv./g.Thespeciﬁc surface area of cellulose and PGTDC-COOH measured by theN2adsorption was29.8and55.1m2/g,respectively.The density ofcellulose and PGTDC-COOH was found to be0.82and1.85g/mL,respectively.3.2.Adsorbent dose on U(VI)adsorptionThe adsorption of U(VI)by cellulose and PGTDC-COOH from U(VI)solution at different adsorbent doses(0.5–5.0g/L)was inves-tigated.The results are shown in Fig.6.Increase in the adsorbentdosage increased the percent removal of U(VI),which is due to theincrease in the surface area of the adsorbent.The complete removalof U(VI)ions from solution containing10mg/L U(VI)was achievedby4and2g/L of cellulose and PGTDC-COOH,respectively.The dataclearly indicate that PGTDC-COOH is two times more effectivethanFig.6.Effect of adsorbent dose on the adsorption of U(VI)onto cellulose and PGTDC-COOH.184T.S.Anirudhan,S.S.Sreekumari/Colloids and Surfaces A:Physicochem.Eng.Aspects361 (2010) 180–186Fig.7.Effect of pH on the adsorption of U(VI)onto PGTDC-COOH. cellulose for the removal of U(VI)from aqueous solution.The high adsorption capacity was probably due to the presence of–COOH groups formed after modiﬁcation.3.3.Effect of pH on U(VI)removalThe pH of the aqueous solution affects the surface charge of the adsorbents as well as the degree of ionization and speciation of the solute.The adsorption of U(VI)on PGTDC-COOH was studied varying the solution pH from2to8.The percentage of adsorption increases with increasing pH value,reaches a maximum at pH6.0 and then remains almost constant(Fig.7).For an initial concen-tration of10and25mg/L,the amount adsorbed was found to be 4.99mg/g(99.9%)and12.12mg/g(97.0%),respectively,at pH6.0. Experimental results show that theﬁnal pH of the solution after adsorption was about4.7when the initial concentration of U(VI) was25mg/L and the original pH was6.0.This also indicates that H+ions are released by exchange mechanism with the removal of U(VI).At low pH,the H+competition with uranium binding sites limits the uptake efﬁciency.At lower pH values the predomi-nant species is UO22+.As the solution pH increases,the uranium speciation in the solution changes and the hydrolysis products such as UO2(OH)+,UO2(OH)22+and(UO2)3(OH)5+are formed[25]. In weakly acidic solution,i.e.,in the range5.0–6.0the dominant species are UO2(OH)+ions which are formed by the hydrolysis of UO22+ions[26].Hence in the pH range,ion exchange followed by complexation is the major mechanism.mPGTDC-COOH+M n+→(PGTDC-COO)m M+n H+(4) where M n+=UO22+and UO2(OH)+.The complex formation was con-ﬁrmed by the peak at930cm−1in the IR spectrum of U(VI)adsorbed PGTDC-COOH which is characteristic of O U O stretching vibra-tion.The pH pzc for PGTDC-COOH was found to be5.6and hence at pH6.0the surface of PGTDC-COOH is slightly negatively charged and the positively charged U(VI)ions are adsorbed on the surface by electrostatic attraction.The variation of surface charge density of PGTDC-COOH with pH and the formation of the hydroxo species reveal that U(VI)ions are adsorbed on PGTDC-COOH by both ion exchange and complexation mechanism.3.4.Effect of contact time and initial concentrationFig.8shows the effect of contact time on the adsorption of U(VI) onto PGTDC-COOH at different initial concentrations.The removal rate of U(VI)was rapid during theﬁrst10min,then increased slowly with the time extension and leveled off at1h.The initial con-centration did not have a signiﬁcant effect on the time to reach equilibrium.The rapid kinetics has signiﬁcant practicalimportance,Fig.8.Effect of contact time and initial concentration on the adsorption of U(VI)onto PGTDC-COOH and comparison of observed data with pseudo-second-order kinetic model.as it facilitates smaller reactor volumes,ensuring high efﬁciency and economy[27].The time proﬁle of U(VI)uptake is a single, smooth and continuous curve leading to saturation suggesting the monolayer coverage of U(VI)on the surface of the adsorbent.The equilibrium adsorption capacity(q e)was12.12,23.17,32.10and 41.20mg/g,respectively,at an initial concentration of25,50,75 and100mg/L,respectively at30◦C.It is evident that the amount of metal ion adsorbed increases with increasing U(VI)concentra-tion.This is due to the increase in the mass driving force which accelerates the diffusion of U(VI)molecules from bulk solution to the adsorbent surface.Thus the initial U(VI)concentration plays an important role in determining the maximum uptake capacity of the PGTDC-COOH for U(VI).3.5.Effect of ionic strengthThe effect of ionic strength on the removal of U(VI)ions from solution was investigated with varying concentrations of NaNO3. The adsorption capacity with NaNO3concentration of0.001,0.005, 0.01,0.05,0.1and0.5M was found to be90.3,87.6,83.3,78.1, 75.6and60.3%,respectively,at an initial U(VI)concentration of 50mg/L.The adsorption decreases with the increase in solution ionic strength.The adverse effect of ionic strength suggests the pos-sibility of ion exchange mechanism in the adsorption of U(VI)ions onto PGTDC-COOH.Adsorption is sensitive to change in the concen-tration of the supporting electrolyte if the electrostatic interaction is very signiﬁcant[28].The reduction in the metal removal percent-age may be due to the presence of Na+ions which can compete with U(VI)ions for the same cation exchange sites of PGTDC-COOH. 3.6.Adsorption kineticsKinetics of adsorption is one of the most attractive character-istics to be responsible for the efﬁciency of adsorption.Since the major mechanism involved in the removal of U(VI)by PGTDC-COOH may be ion exchange followed by complexation,the kinetic data were modeled using pseudo-second-order kinetic model[29].The pseudo-second order rate expression is given bytq t=1k2q e2+tq e(5) where q e and q t are the amount of solute adsorbed per unit adsorbent at equilibrium and time t,respectively.k2is the rate constant for the pseudo-second-order kinetics.The kinetic param-eters estimated are listed in Table1.The value of k2decreases from 4.68×10−2to1.67×10−2g/mg min with an increase in the initialT.S.Anirudhan,S.S.Sreekumari /Colloids and Surfaces A:Physicochem.Eng.Aspects 361 (2010) 180–186185Table 1Kinetic parameters for the adsorption of U(VI)onto PGTDC-COOH.Concentration (mg/L)k 2(g/mg min)q e ,exp (mg/g)q e ,cal (mg/g)R 225 4.68×10−212.1212.320.99950 2.89×10−223.1723.500.99975 1.83×10−232.1332.570.9991001.18×10−241.2041.890.999concentration from 25to 100mg/L.The decrease in the k 2val-ues with increasing concentration might be due to a progressive decrease in covalent interactions,relative to electrostatic interac-tions,of the sites with lower afﬁnity for U(VI)that occurs with increasing initial U(VI)concentration.The correlation coefﬁcient,R 2values (>0.99)for different initial concentrations indicate that the adsorption system belongs to the pseudo-second-order model.Fig.8shows that the theoretical q t values are very close to the experimental values.It is also found that the calculated adsorp-tion amount at equilibrium (q e ,cal )agrees reasonably well with the experimental data in the pseudo-second-order model.Therefore the pseudo-second-order model is suitable to describe the kinetic data.The mechanism involved in the adsorption of U(VI)onto PGTDC-COOH is conﬁrmed as ion exchange followed by complex-ation.For the pseudo-second-order reaction the rate limiting step may be chemisorption,which may involve valency forces through sharing or exchange of electrons between adsorbate and adsorbent.3.7.Adsorption isothermThe analysis of the isotherm data is important to develop an equation which accurately represents the results and could be used for designing purposes.The equilibrium sorption was measured in batch experiments at 30◦C using different initial concentrations varying from 25to 500mg/L at pH 6.0.The sorption isotherm is shown in Fig.9.The shape of isotherm curves corresponded to a L-type curve,according to Giles classiﬁcation [30].In this classiﬁca-tion,type-L assumes a monolayer coverage on the active sites of the surface of the adsorbent and all the adsorption sites are supposed to be equivalent.Hence the adsorption data have been subjected to the Langmuirmodel given by the equation:a e =Q 0bC e1+bC e(6)whereQ 0and b are the Langmuir constants related to maximum adsorption capacity and equilibrium constant or energy of adsorp-tion,respectively.q e is the observed adsorption capacity (mg/g)and C e the equilibrium concentration (mg/L).parison of model ﬁt of the Langmuir model to the experimental data for the adsorption of U(VI)onto PGTDC-COOH.The values of Q 0and b were calculated using non-linear regres-sion analysis and were found to be 99.84mg/g and 0.074L/mg,respectively.Since the correlation coefﬁcient (R 2)value for U(VI)in the present study was 0.987,the experimental data may be regarded to reasonably ﬁt the Langmuir model.The theoretical q e values as calculated from the Langmuir model agree perfectly with the experimental q e values (Fig.9).The applicability of the Langmuir isotherm suggests that the surface of the adsorbent is uniform and homogeneous in respect to sorption and energy,and the adsorption process results in the formation of a monolayer coverage of U(VI).Formation of a monolayer on the adsorbent surface further indi-cates the chemical nature of the adsorption,i.e.,chemisorption.The Q 0values for the adsorption of U(VI)on diatomite [31],natural sepi-olite [32],bacteriogenic iron oxides [33],o-phenylene dioxyacetic acid impregnated amberlite XAD resin [34]and amberlite XAD-4functionalized with succinic acid [35]were reported to be 41.17,34.61,9.25,28.79and 12.30mg/g,respectively.The comparison of Q 0value of PGTDC-COOH used in the present study (99.84mg/g)with those obtained in the literature shows that PGTDC-COOH is more effective for the adsorption process.3.8.Test with simulated nuclear industry wastewaterThe suitability of the adsorbent for the removal of U(VI)from nuclear industry wastewater was tested by treating it with simu-lated wastewater containing U(VI)ions [36].The sample contained metal ions based on cations such as U(VI)(10mg/L),Ca 2+(10mg/L),Mg 2+(10mg/L)as well as anions such as Cl −(20mg/L),SO 42−(80mg/L),NO 3−(40mg/L),PO 43−(20mg/L),oxalate (60mg/L)and detergents (20mg/L).The effect of adsorbent dose on U(VI)removal from wastewater was investigated (Fig.10).The removal of U(VI)increases with increase in the adsorbent dosage due to the avail-ability of more adsorption sites.Almost complete (≈100%)removal from 1L sample was possible with 2.5g/L of PGTDC-COOH.The amount of adsorbent used in this study (2.5g/L)was slightly higher than that obtained in the earlier (Section 3.3)batch experiments (2.0g/L)may be due to the presence of other cations (Ca 2+andMg 2+)in wastewater which can compete with U(VI)ions for the same binding sites of the adsorbent.3.9.Desorption studiesAs illustrated in Fig.7low adsorption was found in the low pH range,which implies that the U(VI)adsorbed can be desorbed from spent adsorbent by an acid medium.Hence desorption study wasFig.10.Effect of adsorbent dose on the adsorption of U(VI)from a simulated nuclear industry wastewater sample by PGTDC-COOH.。

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The performance of polyamide nano ﬁltration membrane for long-term operation in an integrated membrane seawater pretreatment systemYuefei Song,Baowei Su ⁎,Xueli Gao,Congjie GaoKey Laboratory of Marine Chemistry Theory and Technology of Ministry of Education,College of Chemistry &Chemical Engineering,Ocean University of China,238Songling Road,Qingdao,266100,Chinaa b s t r a c ta r t i c l e i n f o Article history:Received 25December 2011Received in revised form 29March 2012Accepted 30March 2012Available online 4May 2012Keywords:Nano ﬁltration seawater softening Ultra ﬁltration pretreatment Integrated membrane system Long-term performance Inorganic fouling Chemical cleaningAn ultra ﬁltration –nano ﬁltration (UF –NF)integrated membrane system (IMS)was operated for 500h to examine the performance of the NF membrane in seawater desalination pretreatment.The rejection of divalent ions,TDS,TOC and UV254by the NF membrane as well as the permeation ﬂux decreased gradually with operating time before each chemical cleaning procedure,while the calculated Stiff and Davis Stability Index (S&DSI)increased gradually from negative up to positive.The result indicates that there exists inorgan-ic fouling during the long run.However,the IMS produced excellent ef ﬂuent with 93.6%removal of total or-ganic carbon (TOC)for long-term operation.The TOC concentration of the NF permeation samples was in the range of 0.06–0.35mg/L.The chemical cleaning results indicated that inorganic fouling should be preferen-tially paid attention to,and a combination of citric acid cleaning and NaOH cleaning may achieve an optimal cleaning ef ﬁciency.The long-term operation reveals that the membrane is more prone to fouling gradually after chemical cleaning.©2012Elsevier B.V.All rights reserved.1.IntroductionThe deposition of undesirable material on membrane surface could cause serious fouling and ﬂux decline of seawater reverse os-mosis (SWRO)membrane.Therefore,it is necessary to ensure that feed water should not cause excessive fouling on SWRO membrane and pretreatment process is needed to provide feed water with better and reliable quality.Proper pretreatment is critical for successful long-term performance of SWRO desalination [1].Conventional pretreatment methods such as ﬂocculation,deep bed ﬁltration and multi-media ﬁltration have been widely applied for sea-water RO plants to remove suspended solids and decrease turbidity and silt density index (SDI)of the feed water [1–3].However,the con-sumption of chemicals in conventional pretreatment is usually very in-tensive,and the quality of the product water is often unstable in operation.Recently,such phenomenon has been reported by several authors [4–6].Teng [4]reported that the quality of the ﬁltrate produced by deep bed ﬁlter was inferior and highly inconsistent.Leparc [5]found that dual-media ﬁlters and cartridge ﬁlters could not reduce content of organic matter with small molecular weight.Obviously,conventional pretreatment processes do not represent a complete barrier to colloids and suspended particles,and they often produce ﬁltrate with unsteady quality and quantity.As a result,the design ﬂux and recovery of SWROmembranes using conventional pretreatment are lowered in order to ensure stable long-term performance.Brehant [6]suggested that the design average ﬂux of RO membrane operating on surface seawa-ter with conventional pretreatment should be limited to about 13.6L.m −2.h −1.UF is an attractive pretreatment technique which could consis-tently reduce turbidity,remove particles and bacteria,and continu-ously produce good quality water at low-pressure levels [7].As a kind of pretreatment technology in seawater desalination,UF can provide high quality ﬁltrate that could totally satisfy the require-ments of SWRO feed quality such as SDI 15and turbidity.Xu [8]reported that excellent quality of UF ﬁltrate with 100%of turbidity below 0.01NTU and 95%of the SDI 15below 3.0could be obtained,which could satisfy the requirement of SWRO feed water completely.Brehant [7]also asserted that the surface seawater SDI of 13–25was reduced to below 1.0using UF pretreatment,whereas the conven-tional pretreatment failed to reduce it below 2.5.The use of UF pro-cess for seawater and wastewater treatment has grown steadily due to its advantages such as no need for chemicals,low pressure,good and constant quality of the treated water in terms of particle and mi-crobial removal,little requirements for raw feed water quality,pro-cess and plant compactness and simple automation.Although UF membranes showed excellent removal ef ﬁciency of particle and high molecular weight organic matter,and could produce ﬁltrate with dissolved organic matter (DOM)ranging from about 1to 2mg/L [9,10],they could not be adequate to remove organic matters with molecular weight in the range of several hundreds due to theirDesalination 296(2012)30–36⁎Corresponding author.Tel./fax:+8653266786371.E-mail address:subaowei@ (B.Su).0011-9164/$–see front matter ©2012Elsevier B.V.All rights reserved.doi:10.1016/j.desal.2012.03.024Contents lists available at SciVerse ScienceDirectDesalinationj o u r n a l h o m e pa ge :w ww.e l se v i e r.c o m/l o c a te /d e sa lrelatively coarse pore size distribution,and it was reported that these low molecular weight organic matters could produce fouling of RO membrane surface[1].NF membrane has a molecular weight cut-off(MWCO)of200–2000Dalton(Da)which can typically reject organic matter with mo-lecular weight greater than approximately200Da[11],and it also has the separation characteristics to remove divalent ions(the ions prone to scaling)effectively.Much research work has been carried out on the utilization of NF membrane for seawater softening.Soﬁ[12]eval-uated the adaptability of the nanoﬁltration technique as pretreatment to provide make-up for multi-stageﬂash(MSF),and the top brine temperature of MSF process could increase up to120°C.Drioli et.al [13]reported that the utilization of NF300PA membrane as pretreat-ment could increase the water recovery of the RO unit in a single ves-sel up to50%.Turek[14]found that at22bar the NF unit could remove hardness ions of Ca2+,Mg2+,SO42−,HCO3−,and total hardness by89.6%,94.0%,97.8%,76.6%and93.3%,separately.Bade[15]adopted NF membrane with30to40%throughput ratio to produce a nearly sulfate-free permeation stream.Saline Water Conversion Corporation (SWCC)applied NF(NF90and NF270)as pretreatment to supply feed water to SWRO and concluded that NF exhibited excellent perfor-mance as seawater softening technology[16].However,in most of the above research work,UF pretreatment was not used for NF feed. As integrated membrane system(IMS)utilizing multiple membranes with different characteristics can lower the membrane fouling rates and results in more stable operation[17],it is signiﬁcant to adopt UF–NF systems as integrated pretreatment techniques for seawater softening.However,there is a need to predict the permeationﬂuxes and rejections during long-term operation for the purpose of process design,optimization and economic assessment.In this study,long-term test was conducted with coastal seawater to investigate the performance stability of NF membrane.The aim of this study was to assess an UF–NF integrated membrane system for surface seawater desalination pretreatment,and determine the efﬁ-ciency of the integrated membrane system and evaluate the perfor-mance of NF membrane through a long-term investigation.2.Material and methods2.1.MembranesA tight UF membrane(MWCO20,000Da)and an ultra-low-pressure NF membrane(ESNA3,Hydranautics)were adopted as an appropriate pretreatment membrane system for long-term perfor-mance.The properties of the selected UF and NF membrane module were summarized in Table1.ESNA3has great advantage for the se-lectivity of divalent ions over monovalent ions.According to the ex-perimental data[18],the ion selectivity of ESNA3membrane lies in the range of3.9and4.8.2.2.Long-term pretreatment procedure2.2.1.Schematic diagram of the pilot-scale UF–NF integrated membrane systemSchematic diagram of the pilot-scale UF–NF integrated membrane system(IMS)was shown in Fig.1.This process was used to soften coast-al seawater having a total dissolved solids(TDS)of about25,000–40,000mg.L–1at Jiaozhou Bay,Qingdao,China.This pilot system with capacity of8–10m3·d–1consists of UF system(raw seawater pump, sandﬁlter,feed tank,UF feed pump,hollowﬁber UF modules,backwash system)and NF system(feed tank,low-pressure pump,high-pressure pump,spiral-wound NF module,permeation tank).Raw seawater was pumped through cartridge sandﬁlter to remove particles that could block the UFﬁber.Theﬁltrate water was then fed to the UF membrane unit.A high pressure pump delivered the UFﬁltrate to the NF mem-brane unit.Operational data including temperature,pressure,pH,as well as conductivity andﬂowrate of the product and brine were monitored periodically by on-line instruments,and permeationﬂux was calcu-lated.The data presented here covered a period of500h starting from October2009,and all the operation conditions of the NF mem-brane were kept at temperature of23±1°C,pressure of 2.05±0.02MPa and cross-ﬂow velocity of0.035m.s–1.2.2.2.Operating parameters of UF processThe operating parameters of UF process used in the long run were optimized in our former research work[8],and were kept constant which are given in Table2.2.2.3.Key operational considerations for IMSThe key operational considerations for integration of the membrane processes in this work includeﬂux,salt rejection,and removal of organ-ic matter,S&DSI,pressure requirements,and long-term performance.According to solution–diffusion model,waterﬂux through NF membrane and salt rejection are described as[19]:R¼1−c p=c fÂ100%ð1Þwhere c p and c f represent concentrations on permeation and feed sides.The S&DSI index is widely used to predict the precipitation of calcium carbonate on seawater reverse osmosis membrane.This index is deﬁned as the pH of solution minus the pH of the solution in equilibrium with calcium carbonate.The equation of S&DSI is[20]: S&DSI¼pH−pH Sð2ÞpH S¼pCaþpAlkþKð3Þwhere pH is the pH of the concentrate,and pH S is the pH at which concentration reaches saturation with calcium carbonate.pCa is the negative log concentration of calcium,pAlk is the negative log total al-kalinity,and K is a constant which depends on the salinity and tem-perature.The S&DSI of Eq.(2)is an index of stability that,when positive,indicates the possible precipitation of calcium carbonate.If the value is negative,it indicates that no calcium carbonate scaling would occur.2.3.Analytical methodsMeasurements of water quality including TOC,UV254,conductivity, main ions(K+,Na+,Ca2+,Mg2+,Cl−,SO42−)and turbidity are pre-sented as follows:The TOC of permeation samples from the UF–NF integrated membrane process was analyzed using a TOC-5000A analyz-er(Shimadzu,Japan).The organic matter concentration for each sample was also analyzed using an Ultraviolet/visible spectrophotometerTable1Details of the membrane modules.Items UF NFManufacturer Lanlu(China)Hydranautics Module type HF-1500ESNA3,4040 Module conﬁguration Hollowﬁber Spiral wound Membrane materials PS Polyamide Molecular weight cut-off(Da)20,000100–500 Membrane effective area(m2)87.9Pure waterﬂux(L.m−2·h−1·MPa−1)2419.353.5Pore size(nm)101Salt rejection(%)≈0>25%⁎Range of feed temperature(°C)0–500–45Range of feed pH2–112–11Range of operational pressure(MPa)0–0.20–4.0⁎Testing parameters:0.048MPa,25°C,500mg/L NaCl solution,the recovery rate 15%.31Y.Song et al./Desalination296(2012)30–36(Shimadzu's Uv-2550,Japan)at a wavelength number of 254nm [21].To measure water quality parameters such as TOC and UV 254(UV absor-bance at 254nm)in the in ﬂuent seawater and the permeation water,each sampling was at an interval of about 4h,and the samples were pretreated with high-frequency sound waves (40W)for 3min.The concentrations of the main inorganic ions (K +,Na +,Ca 2+,Mg 2+,Cl −,SO 42−)were analyzed using an ion chromatographic analyzer (DIONEX-3000,America).The conductivity and turbidity values were measured with a conductivity meter (Thermo's Orion 145A+,USA)and turbidity meter (HANNA's LP-2001,Italy),respectively.2.4.Chemical cleaning processesChemical cleaning was adopted when the NF permeation ﬂux declined over 10%during the long run.The fouled membrane was washed with different cleaning agents for 30min at atmospheric pressure,respectively.Chemical cleaning was performed twice,using 2.0wt.%citric acid and 0.1wt.%NaOH in sequence at atmo-spheric temperature.The chemical agents were chosen according to the protocol proposed by the manufacturer,and also the foulants possibly present in feed water [22].The effect of acid and alkali cleaning on the cleaning ef ﬁciency was investigated.The ﬂux of the membrane before and after fouling was measured at temperature of 23±1°C,pressure of 2.05±0.2MPa and cross-ﬂow ve-locity of 0.035m.s –1with UF ﬁltrate.The initial water permeation ﬂux was denoted as j wi .When the permeation ﬂux declined over 10%,the membrane was washed with two cleaning agents at 23±1°C and at-mospheric pressure,respectively.Citric acid cleaning was ﬁrst per-formed for half an hour,and then the membrane was soaked by the acid solution for half an hour.After that,the solution was ﬂushed out thoroughly by UF ﬁltrate for 5min to remove any chemical agent,and the membrane ﬂux was measured at the same measuring condition of j wi and denoted as j w,acid .Then the membrane was cleaned by NaOH for half an hour,and soaked for another half hour with the base solution.These were followed by a wash with UF ﬁltrate for 5min to remove any chemical agent.Afterward,the long run was continued with UF ﬁltrate and the ﬂux after chemical cleaning was measured again at the same measuring condition of j wi during the beginning half hour and denoted as j wc .Resistance removal rate (RR )[23–25]and ﬂux recovery (FR )[26]were used to understand the cleaning ef ﬁciency.RR %ðÞ¼R f −R c ðÞ=R f ½ Â100ð4ÞFR %ðÞ¼j wc =j wi ðÞÂ100ð5Þwhere R f is the resistance after fouling and R c is the resistance after cleaning.3.Results and discussion3.1.Long-term stability of the NF membrane for inorganic matters 3.1.1.Variation of permeation ﬂux and transmembrane pressure with timeThe results of the long-term performance of the NF membrane and the two short chemical cleaning periods (after 280h and 440h of ﬁl-tration,respectively)during a period of 500h were shown in Figs.2and 3.As can be seen from Fig.2,operating pressure was kept constant at 2.03MPa during the ﬁrst ﬁltration period (before 280h),and in-creased to 2.05MPa (the second ﬁltration period,before 440h)and 2.06MPa (the ﬁnal ﬁltration period),respectively,after twice chemi-cal cleanings.The gradually increased operating pressure indicated that there maybe a little fraction of fouling which could hardly be cleaned in conjunction with chemical cleaning.It can also be seen from Fig.2that both the permeation ﬂow rate and brine ﬂow rate de-creased during each ﬁltration period.The variation of the ﬂux and recovery of NF membrane module with time were depicted in Fig.3.The recovery of NF membrane descended gently during the ﬁrst ﬁltration period,which means that the ﬂow rate of the permeation water declined more signi ﬁcantly than that of the brine while the permeation ﬂux decreased from 43.0L.m −2.h −1at the beginning to a steady state of 38.4L.m −2.h −1,indicating an ap-proximately 10%decline due to membrane fouling.Membrane was judged to lose its ef ﬁciency while the permeation ﬂux was less than 90%of initial ﬂux.The ESNA3NF membrane lost its ef ﬁciency after 280h and 440h of operation,respectively.Chemical cleanings were adopted immediately at these two spots,and the long-term stability of NF membrane was signi ﬁcantly improved.The two short chemical cleaning periods are shown in Figs.2and 3.The membrane ﬂuxes were recovered 97.5%and 95.8%of j wi after the two cleanings,respectively,showing that a little fraction of foul-ing substance was tightly bound to the membrane surface.3.1.2.Rejection of saltSalt rejection is an important factor to evaluate the electrostatic repulsion property of the NF membrane.For charged NF membranes,the performance of ion separation is controlled primarily by Donnan exclusion effect which increases with membrane charge [27].BecauseSand FilterNF Feed Tank NF ModuleLP Pump HP Pump Cartridge Filter LP Pump UF Module LP Pump Fig.1.Schematic diagram of the pilot-scale UF –NF integrated membrane system.Table 2Operating parameters of UF process.ParametersValues ParametersValues Feed pressure (MPa)0.06Permeate SDI 152.2–2.8Permeate pressure (MPa)0.02Permeate turbidity (NTU)0–0.02Permeate ﬂow (L.h -1)1000Filtration duration (min)30Recovery (%)80Flush duration (min)1Feed temperature (°C)23Backwash duration (min)0.532Y.Song et al./Desalination 296(2012)30–36ion strength is too high in seawater,Donnan exclusion mechanism could not be used to explain the observation from a view of surface charge.Salt rejection by NF membrane could be in ﬂuenced by the combination of the size exclusion and diffusion control theories [28].During the long-term operation,the salt rejection (calculated by conductivity and TDS,respectively)was measured (Fig.4a and b).The rejection rate of conductivity for the ﬁrst period,the second period and the third period decreases from 15.0%,14.5%and 14.3%to 8.3%,9.8%and 13.39%,respectively.The rejection rate of TDS by the NF membrane decreased from 23.6%to 19.9%during the ﬁrst pe-riod.Similar results were found in the other period of the procedure.This phenomenon also existed sometimes when the ﬂux after cleaning was higher than that of the virgin untreated membrane [29].It indicated that although the cleaning ef ﬁciency was excellent and the operating ﬂux may be higher than the initial ﬂux,serious membrane fouling could even occur with the ongoing of the experi-ment but not be detected by ordinary examination.Therefore,the judgment of membrane ef ﬁciency loss and membrane fouling simply by indication of ﬂux decline may be inadequate.The result in Fig.4implies that the rejection variation of the solution conductivity might be a convenient and proper method to indicate the membrane fouling during long-run.Similar to the removal ef ﬁciency of the conductivity and TDS,the inorganic ions rejection rates also decreased gradually during each operating period (Fig.5and Table 3).The results show that ESNA3membrane attained signi ﬁcant removals of Mg 2+,Ca 2+and SO 42−.However,the rejections of these ions steadily decreased with the op-eration continued in a manner similar to the trend of salt rejection (calculated by conductivity and TDS,respectively)for each period,as was discussed previously [18].The ESNA3membrane appeared tobe incapable of removing Na +,K +and Cl −,and the rejections of monovalent ions are quite lower than 20%.The large difference of salt rejection of monovalent and divalent ions may be due to the ste-ric effect and the dielectric exclusion [27],the stokes radius is higher for both divalent ions than for Na +or Cl −ions,then the divalent ions are more rejected than the monovalent ions that can go through the very narrow pores of the membrane.Silva [30–32]reported that the dielectric exclusion energy is higher for divalent ions than for mono-valent ones.Therefore the dielectric effect at the interfaces contrib-utes to the better separation of the divalent ions too.Operating time (h)F l u x (L .m -2h -1)R e c o v e r y (%)Fig.3.The variation of water ﬂux and recovery of NF membrane with operating time.Operating time (h)C o n d u c t i v i t y (m s .c m -1)aR e j e c t i o n (%)Operating time (h)T o t a l d i s s o l v e d s o l i d s (m g .L -1)R e j e c t i o n (%)bFig.4.The variation of TDS and conductivity of feed water and permeate;and the rejec-tion with operating time.R e j e c t i o n (%)Operating time (h)Fig.5.The variation of rejection of main ions in seawater with operatingtime.Operating time (h)F l o w r a t e (L .h -1)O p e r a t i n g p r e s s u r e (M P a )Fig.2.The variation of ﬂowrate and pressure of NF membrane with operating time.33Y.Song et al./Desalination 296(2012)30–363.1.3.Calculation of S&DSIThe concentrations of main ions in the brine were measured for cal-culating S&DSI,and the results are plotted versus operating time in Fig.6.It can be seen that the brine S&DSI increases from about −0.4up to about 0.25or higher for the ﬁrst and the second period.During ini-tial 180h,the values of S&DSI in the brine are always negative,which indicates that calcium carbonate scaling could not be formed on the membrane surface.But this value increased from −0.06at hour 175to 0.25at hour 275,indicating that part of calcium carbonate in the brine gradually deposited on the membrane,causing more and more serious inorganic fouling during this testing period.Maybe it is due to the pH of the brine that ascends from 7.9to 8.2gradually in the long runs.As also could be observed in Fig.6,the occurrence of scaling is much easier in the second and the ﬁnal period than in the ﬁrst period.This phenomenon might be attributed to the modi ﬁcation of the NF membrane surface material and structure by the chemical cleanings.This could also be explained by the gradually decrease of the inorganic ion rejection rates with operating time.3.2.Long-term stability of the NF membrane for organic matter removal Each sample was subjected to the measurements of TOC as well as UV 254to calculate organic matter concentration.The evolution of TOC concentrations in the NF feed water samples,the NF permeation sam-ples,and raw seawater samples was shown in Fig.7.The average TOC in the NF feed water samples and raw seawater samples during the op-eration was 1.05±0.10and 2.40±0.35mg.L -1,respectively.However,the TOC concentration of the NF permeation samples was in the range of 0.06–0.35mg.L -1,which suggested that the selected NF membrane could produce permeation with very good quality for a long-term oper-ation even though the ﬂux decreased to approach 90%.During each pe-riod,the TOC values in the NF permeation samples increased gradually,which indicated that the removal ef ﬁciency of TOC by the NF membrane decreased with the operating time gradually.Organic matter was removed by the IMS through two functional units,UF and NF respectively.UF membrane module is on molecule-sieving mechanism,and NF membrane module is on solution –diffusion mechanism.The average TOC removal ef ﬁciency of the IMS was about 93.6%,among which,53.7%of the TOC was removed by the UF and the residual was removed by the NF membrane ﬁltration.The TOC rejection of the NF membrane was declined from more than 90%to lower than 80%during each period,indicating that the NF membrane fouling is be-coming severe gradually.Nevertheless,the NF membrane remained high rejection of TOC,which indicated that NF played a signi ﬁcant role in UF –NF IMS organic removal irrespective of variation of raw seawater concentrations.To certify whether the organic matter in permeation water in-creased gradually over operating time,the UV 254values (including raw seawater,the feed water and the permeation of the NF mem-brane)were measured along with operating time (Fig.8).As a conse-quence,UV 254rejection for the ﬁrst period,the second period and the ﬁnal period decreases from 92.1%,89.1%and 90.3%to 72.2%,80.2%and 88.2%,separately.There is still a little amount of organic matter remaining in the NF permeation water,it is denoted as low molecular weight organic matter (LMWOM)which can produce new fouling on RO membrane surface.However,the LMWOM content is much less after NF ﬁltration,therefore RO membrane organic and biological fouling potential could be anic matter concentration before and after UF/NF ﬁltration was summarized in Table 4.It could be seen that the organic matter rejection by the NF membrane in hour 280was lower obviously than that in hour 30.Owing to the fact that UV 254is a much cheaper and convenient method to re ﬂect membrane organic fouling,and sometimes the ap-parent ﬂux could not re ﬂect the fouling conditions directly because of the seasons variation of the seawater temperature,therefore,weTable 3Main characteristics of waters before and after NF ﬁltration.ParametersHour 30Hour 280Hour 470NF feedwaterNF permeation NF feedwater NF permeate NF feedwater NF permeation TDS (mg.L -1)33,76025,50034,51027,19033,94025,810Total hardness (mg/L as CaCO 3)633025046513297363332708Ca 2+(mg.L -1)409267413287411328Mg 2+(mg.L -1)129544713375501294460SO 42−(mg.L -1)231024230437227530Na +(mg.L -1)10,985909811,261973011,0619448Cl −(mg.L -1)18,16215,14518,92716,12718,73015,869pH8.2 6.08.0 6.28.1 6.0Flow rate (m.s -1)0.03500.03500.0350TMP (MPa)2.032.052.06S &D S I [-]Operating time (h)Fig.6.Variance of S&DSI of NF brine with operatingtime.Operating time (h)T O C (m g .L -1)R e j e c t i o n o f o r g a n i c m a t t e r b y N F (%)Fig.7.The variation of TOC and organic matter rejection with operating time.34Y.Song et al./Desalination 296(2012)30–36suggest that UV 254be used to indicate the membrane organic fouling during long-run.3.3.Fouling and cleaning of the NF membraneThe effect of chemical cleaning on FR and RR of the fouled mem-brane was investigated.The in ﬂuence of citric acid cleaning and NaOH cleaning on NF membrane recovery at 23°C,cross-ﬂow veloc-ity of 0.035m/s and ambient pressure was shown in Fig.9.As can be seen from Fig.9,the cleaning ef ﬁciency of citric acid,NaOH and the overall in terms of FR was 80.5%,17%and 97.5%,respec-tively,for the ﬁrst chemical cleaning,while in terms of RR ,it was 80.2%,13.2%and 93.4%,respectively.Citric acid exhibits the higher cleaning ef ﬁciency,which indicates that inorganic fouling potential was more severe than organic fouling potential during the long-term operation.Comparing the ﬁrst chemical cleaning with the second chemical cleaning,it could be found obviously from Fig.9that under the same cleaning procedure,the ﬁrst chemical cleaning yields the higher ef ﬁciency in terms of both FR and RR than the second.The cleaning ef-ﬁciency of citric acid,NaOH and the overall in terms of FR was 78.7%,17.1%and 95.8%,respectively,in the second chemical cleaning.This could be explained by the fact that as the operating time increases,the j wc after the ﬁrst chemical cleaning was higher than the value after the second chemical cleaning.The effect of the second chemical cleaning is not so ef ﬁcient than the ﬁrst,as shown in Fig.9.This phenomenon can also be indicated from Figs.2to 7,in which it could be found that all the rejections of the conductivity,TDS and TOC of the NF membrane decreased rela-tively more sharply and the S&DSI index increased relatively more apparently in the second period than in the ﬁrst period,which phe-nomena could only be found in the long-term operation.It re ﬂects the effect of membrane fouling on the performance of the NF mem-brane and indicates that membrane fouling is becoming faster during the long run and the membrane is more prone to fouling gradually after chemical cleaning.It also can be deduced from Fig.9that inorganic fouling should be preferentially paid attention to for NF seawater softening during chemical cleaning due to the inorganic components contained in the feed water (average TDS 35000mg.L -1).It is well known that acid such as the widely used citric acid is essential for recovering membrane performance impaired by the accumulation of inorganic foulants on membrane surface or in pores.However,with average 2.4mg/L TOC ex-ists in the feed water,if not combined with other agents,citric acid so-lution is ineffective due to the organic foulants.The results indicate that a combination of NaOH cleaning and citric cleaning may achieve an op-timal cleaning ef ﬁciency.4.ConclusionsAn UF –NF integrated membrane system was operated for 500h to examine the performance of the polyamide ESNA3NF membrane in seawater desalination pretreatment for long-term operation.(1)Rejection rates of monovalent and divalent ions by the NFmembrane,as well as the permeation ﬂux gradually decreased during each chemical cleaning interval due to the membrane fouling.The S&DSI values in the experiments increased from about −0.4up to about 0.25or higher before each chemical cleaning,indicating that part of calcium carbonate in the brine gradually deposited on the membrane,causing more and more serious inorganic fouling during this testing period.(2)The IMS produced better ef ﬂuent with 93.6%TOC removal forlong-term operation.The TOC concentration of the NF perme-ation samples was in the range of 0.06–0.35mg/L,indicating that the NF membrane could produce very good-quality per-meation for a long-term operation.(3)Rejection variation of conductivity might be a convenientmethod to indicate the membrane fouling during long-run.(4)Both the increase of the TOC and UV 254indicate that mem-brane is fouling gradually during the long run,and compared with TOC,UV 254is a much cheaper and convenient method that could be used to indicate the membrane organic fouling during long-run.(5)The long-term operation reveals that all the rejections of theconductivity,TDS and TOC of the NF membrane decreased rel-atively more sharply and the S&DSI index increased relatively more apparently in the second period than in the ﬁrst period,which re ﬂect the effect of membrane fouling on the perfor-mance of the NF membrane and indicate that membrane foul-ing is becoming faster during the long run and the membrane is more prone to fouling gradually after chemical cleaning.(6)Inorganic fouling should be preferentially paid attention toduring chemical cleaning due to the inorganic componentsOperating time (h)U V 254 (c m -1)O r g a n i c m a t t e r r e j e c t i o n (%)Fig.8.The variation of UV254and organic matter rejection with operating time.Table 4Organic matter concentration before and after UF/NF ﬁltration.Hour 30Hour 280Hour 470TOC (mg.L -1)UV 254(cm -1)TOC (mg.L -1)UV 254(cm -1)TOC (mg.L -1)UV 254(cm -1)Raw seawater 2.080.05 2.520.052 2.360.054NF feedwater 0.940.18 1.060.0180.970.02NF permeate 0.060.0010.340.0050.090.002Rejection0.9360.9940.6790.7220.9070.900100F R , R R (%)Acid cleaningFig.9.Effect of different types cleaning agents on FR and RR.35Y.Song et al./Desalination 296(2012)30–36。