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InternationalJournalofPharmaceutics456 (2013) 49–57
ContentslistsavailableatScienceDirect
InternationalJournalof
Pharmaceutics
journalhomepage:www.elsevier.com/locate/ijpharm
Theeffectoflipidcompositionandliposomesizeontherelease
propertiesofliposomes-in-hydrogel
JuliaHurlera,SimonˇZakeljb,JanezMravljakb,StanePajkb,c,AlbinKristlb,
RolfSchubertd,NataˇsaˇSkalko-Basneta,∗
aUniversityofTromsø,DrugTransportandDeliveryResearchGroup,DepartmentofPharmacy,Universitetsveien57,N-9037Tromsø,NorwaybUniversityofLjubljana,FacultyofPharmacy,Aˇskerˇcevacesta7,SI-1000Ljubljana,SloveniacInstitutJoˇzefStefan,LaboratoryofBiophysics–EPRcenter,Jamova39,SI-1000Ljubljana,SloveniadAlbertLudwigUniversity,DepartmentofPharmaceuticalTechnologyandBiopharmacy,Hermann-Herder-Straße9,D-79104Freiburg,Germany
articleinfo
Articlehistory:Received19June2013Receivedinrevisedform9August2013Accepted12August2013Available online 27 August 2013
Keywords:LiposomesHydrogelsInvitroreleaseChitosanSkintherapyabstract
Tostudythereleaseofliposome-associateddrugsintohydrogels,wedesignedandsynthesizedtwopH-sensitiverhodaminederivativestouseasmodelcompoundsofdifferentlipophilicities.Thedyeswerefluorescentwheninthefreeformreleasedfromliposomesintothechitosanhydrogel,butnotwhenincorporatedwithinliposomes.Theeffectofliposomalcomposition,surfacechargeandvesiclesizeonthereleaseofthoseincorporateddyeswasevaluated.Thelipophilicityoftherhodaminederivativesaffectedboththeamountandrateofrelease.Whileliposomesizehadonlyaminoreffectonthereleaseofdyesintothehydrogel,thesurfacechargeaffectedthereleasetoagreaterextent.Byoptimizingthecharacteristicsofliposomeswecoulddevelopaliposomes-in-hydrogelsystemforapplicationinwoundtherapy.Wefurthercharacterizedliposomes-in-hydrogelfortheirrheologicalproperties,texturesandmoisturehandling,aswellastheirpotentialtoachieveacontrolledreleaseofthedye.Thepolymer-dependentchangesinthehydrogelpropertieswereobserveduponadditionofliposomes.Thechargedliposomesexhibitedstrongereffectsonthetexturesofthechitosanhydrogelsthantheneutralones.Inrespecttotheabilityofthesystemtohandlewoundexudates,chitosan-basedhydrogelswerefoundtobesuperiortoCarbopol-basedhydrogels.© 2013 Elsevier B.V. All rights reserved.
1.Introduction
Amajoraiminthedevelopmentofmodernhydrogelfor-
mulationssuchasthosecurrentlyusedinwounddressings,is
toachievetheeffectiveandaccuratedeliveryoftherequired
therapeuticagentsincludedintheformulationoveraprolonged
periodoftime(Boatengetal.,2008).Amonghydrogels,chitosan
hydrogelsareoneofthemoststudiedsystems,particularlywith
respecttotheirbioadhesiveness.Chitosanhasfrequentlybeen
studiedasapossiblewounddressingandasadeliverysystemfor
Abbreviations:ns,non-sonicated;PC,phosphatidylcholine;PCns,non-sonicatedphosphatidylcholineliposomes;PCs,sonicatedphosphatidylcholineliposomes;PC/PG,phosphatidylcholine/phosphatidylglycerol;PC/PGns,non-sonicatedphosphatidylcholine/phosphatidylglycerolliposomes;PC/PGs,sonicatedphosphatidylcholine/phosphatidylglycerolliposomes;PC/SA,phosphatidylcholine/octadecylamine;PC/SAns,non-sonicatedphosphatidyl-choline/octadecylamine;PC/SAs,sonicatedphosphatidylcholine/octadecylamine;PG,phosphatidylglycerol;PI,polydispersityindex;s,sonicated;SA,octadecylamine(=stearylamine).∗Correspondingauthor.Tel.:+4777646640;fax:+4777646151.E-mailaddress:natasa.skalko-basnet@uit.no(N.ˇSkalko-Basnet).therapeuticagents.Thisisprimarilyduetoitsconfirmedbiocom-
patible,biodegradable,non-toxicandbacteriostaticproperties,
aswellasitsabilitytopromotewoundhealing(Denisetal.,
2012).Whilealotofresearchonthepotentialuseofchitosan
asawounddressinghasfocusedonplainchitosanhydrogels,
chitosan-basedhydrogels(Alsarra,2009;Bhattaraietal.,2010;
Ribeiroetal.,2009),chitosanfilms(Aoyagietal.,2007;Noeletal.,
2008)andotherchitosan-basedformulations(Salametal.,2010),
relativelylittlehasbeenpublishedaboutliposomalchitosan
hydrogels.
Therationalebehindusingliposomes-in-hydrogelasadelivery
systemistoassuresustaineddrugreleaseduringtheirprolonged
presenceattheadministrationsite(Ruel-Gariepyetal.,2002).The
releaseofdrugsfromdrugs-in-liposomes-in-hydrogelsystemsis
affectedbydifferentfactorsrelatedtothephysicochemicalproper-
tiesofthedrug.Thereleaseofamphiphilic/lipophilicdrugs,which
areassumedtohavetheabilitytopenetratetheliposomalmem-
brane,willbedeterminedbythelipidconcentrationofliposomes
addedintothegel(Mourtasetal.,2008b).
Inthecurrentstudyweaimedtogainabetterinsightintothe
interactionsbetweendrugmolecules,liposomesandhydrogels.
However,thecomplexityoftheliposomes-in-hydrogeldelivery
0378-5173/$–seefrontmatter© 2013 Elsevier B.V. All rights reserved.http://dx.doi.org/10.1016/j.ijpharm.2013.08.033
