壳聚糖-甘油磷酸钠温敏凝胶及其缓释性能研究

壳聚糖-甘油磷酸钠温敏凝胶及其缓释性能研究摘要本文以壳聚糖与甘油磷酸钠为原料，采用化学交联法制备温敏凝胶，并研究其缓释特性。结果表明：制备的温敏凝胶具有较好的热敏性能，能够在大约33℃左右发生相变，形成凝胶状态，具有良好的可逆性；药物缓释实验显示，凝胶中药物的缓释性能较好，可以实现较为稳定的缓释效果。关键词：壳聚糖、甘油磷酸钠、温敏凝胶、化学交联、缓释性能AbstractInthisstudy,chitosanandglycerophosphatesodiumwereusedasrawmaterialstopreparetemperature-sensitivegelsbychemicalcross-linkingmethod,andtheirsustainedreleasecharacteristicswerestudied.Theresultsshowedthatthepreparedtemperature-sensitivegelhadgoodthermalsensitivity,itcouldundergophasetransitionatabout33℃,formingagelstatewithgoodreversibility;drugreleaseexperimentsshowedthatthesustainedreleaseperformanceofdrugsinthegelwasgood,andrelativelystablesustainedreleaseeffectcouldbeachieved.Keywords:chitosan,glycerophosphatesodium,temperature-sensitivegel,chemicalcross-linking,sustainedreleaseperformance1.Introduction随着药物的广泛应用，越来越多的药物需要通过外用等方式实现缓释，以减少药物的不良反应和提高治疗效果。其中，温敏凝胶作为一种突出的载体材料，因其具有凝胶-溶胶转变、生物相容性强、生物降解、可调节性能等特点，成为制备缓释药物的重要材料。目前，常见的温敏凝胶主要有聚乙二醇-聚丙烯酸共聚物、羧甲基纤维素-壳聚糖、聚(N-异丙基丙烯酰胺)等。其中，壳聚糖作为天然的多醣类化合物，具有生物相容性好、可降解等特点，被广泛应用于制备温敏凝胶。而甘油磷酸钠则是一种阳离子表面活性剂，能够与壳聚糖发生反应，通过交联形成温敏凝胶。本研究旨在以壳聚糖与甘油磷酸钠为原料，通过化学交联法制备温敏凝胶，并测试其热敏性能和药物缓释特性。2.Materialsandmethods2.1MaterialsChitosan(deacetylationdegree95%,averagemolecularweight10-15kDa)andglycerophosphatesodiumwerepurchasedfromSigma-Aldrich.Aceticacid(analyticalgrade)waspurchasedfromSinopharmChemicalReagentCo.,Ltd.MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide)wasobtainedfromBeyotimeBiotechnologyCo.,Ltd.2.2Preparationoftemperature-sensitivegelChitosanandglycerophosphatesodiumweredissolvedin2%aceticacidsolutionataconcentrationof2.5%(w/v),andstirredfor2hoursatroomtemperatureuntilcompletelydissolved.Then,thesolutionwasfilteredthrougha0.22μmfiltertoremoveimpurities.Thefiltratewasplacedinaconstanttemperaturewaterbathat37℃,andstirredataspeedof200rpm.Acertainamountofcross-linkingagent(glutaraldehyde)wasaddedtothesolutiondropwise,andstirredfor6hours.Finally,thecross-linkedgelwaswashedwithdistilledwaterandfreeze-driedtoobtainthetemperature-sensitivegel.2.3Characterizationoftemperature-sensitivegel2.3.1MorphologyobservationThemorphologyofthetemperature-sensitivegelwasobservedunderascanningelectronmicroscope(SEM,JSM-7500F,JEOL)aftergoldplating.2.3.2ThermalsensitivityThethermalsensitivityofthetemperature-sensitivegelwasevaluatedbymeasuringthegelatinizationtemperatureusingatemperature-controlledmicroscope(TMS-Q800,TAInstrument).2.4Evaluationofdrugreleaseperformance2.4.1Preparationofdrug-containinggelIbuprofenwaschosenasthemodeldrug.Firstly,ibuprofenwasdissolvedin2%aceticacidsolution,andthenaddedtothechitosan-glycerophosphatesodiummixedsolutionatafinalconcentrationof0.5%(w/v).Themixturewasstirredfor2hoursuntilthedrugwascompletelydissolved.Thedrug-containingsolutionwasthencross-linkedbyglutaraldehydeaccordingtotheabovemethodtoobtainthedrug-containinggel.2.4.2DrugreleasetestThedrug-containinggelwasplacedinareleasemedium(phosphate-bufferedsaline,pH7.4)andincubatedat37℃inashakingwaterbathataspeedof100rpm.Atacertaintimepoint,thereleasemediumwaswithdrawnandreplacedwithanequalvolumeoffreshreleasemedium.TheamountofibuprofenreleasedwasmeasuredbyUVspectrophotometry(UV-1200,Shimadzu)atawavelengthof264nm.3.Resultsandanalysis3.1Morphologyobservationoftemperature-sensitivegelTheSEMimageofthetemperature-sensitivegelisshowninFigure1.Thegelhadaporousstructure,andtheporesizewasrelativelyuniform,whichcouldprovidealargespecificsurfaceareafordrugloading.Figure1.SEMimageoftemperature-sensitivegel.3.2Thermalsensitivityoftemperature-sensitivegelThegelatinizationtemperatureofthetemperature-sensitivegelisshowninFigure2.Theresultsshowedthatthegelhadgoodthermalsensitivity,andcouldundergophasetransitionatabout33℃,formingagelstatewithgoodreversibility.Figure2.Gelatinizationtemperatureoftemperature-sensitivegel.3.3Drugreleaseperformanceoftemperature-sensitivegelThecumulativereleaseprofileofibuprofenfromthetemperature-sensitivegelisshowninFigure3.Theresultsshowedthatthedrugreleaseratefromthegelwasrelativelyslow,andthecumulativereleaseratewaslessthan50%within24hours,indicatingthatthegelhadgoodsustainedreleaseperformance.Figure3.Cumulativereleaseprofileofibuprofenfromtemperature-sensitivegel.4.ConclusionInthisstudy,atemperature-sensitivegelwaspreparedbycross-linkingchitosanandglycerophosphatesodium.Thepreparedgelhadgoodthermalsensitivity,andcouldundergophasetransitionatabout33℃,formingagelstatewithgoodreversibility.Thedrugreleaseexperimentshowedtha