殼聚糖-甘油磷酸鈉溫敏凝膠及其緩釋性能研究摘要本文以殼聚糖與甘油磷酸鈉為原料，采用化學(xué)交聯(lián)法制備溫敏凝膠，并研究其緩釋特性。結(jié)果表明：制備的溫敏凝膠具有較好的熱敏性能，能夠在大約33℃左右發(fā)生相變，形成凝膠狀態(tài)，具有良好的可逆性；藥物緩釋實(shí)驗(yàn)顯示，凝膠中藥物的緩釋性能較好，可以實(shí)現(xiàn)較為穩(wěn)定的緩釋效果。關(guān)鍵詞：殼聚糖、甘油磷酸鈉、溫敏凝膠、化學(xué)交聯(lián)、緩釋性能AbstractInthisstudy,chitosanandglycerophosphatesodiumwereusedasrawmaterialstopreparetemperature-sensitivegelsbychemicalcross-linkingmethod,andtheirsustainedreleasecharacteristicswerestudied.Theresultsshowedthatthepreparedtemperature-sensitivegelhadgoodthermalsensitivity,itcouldundergophasetransitionatabout33℃,formingagelstatewithgoodreversibility;drugreleaseexperimentsshowedthatthesustainedreleaseperformanceofdrugsinthegelwasgood,andrelativelystablesustainedreleaseeffectcouldbeachieved.Keywords:chitosan,glycerophosphatesodium,temperature-sensitivegel,chemicalcross-linking,sustainedreleaseperformance1.Introduction隨著藥物的廣泛應(yīng)用，越來越多的藥物需要通過外用等方式實(shí)現(xiàn)緩釋，以減少藥物的不良反應(yīng)和提高治療效果。其中，溫敏凝膠作為一種突出的載體材料，因其具有凝膠-溶膠轉(zhuǎn)變、生物相容性強(qiáng)、生物降解、可調(diào)節(jié)性能等特點(diǎn)，成為制備緩釋藥物的重要材料。目前，常見的溫敏凝膠主要有聚乙二醇-聚丙烯酸共聚物、羧甲基纖維素-殼聚糖、聚(N-異丙基丙烯酰胺)等。其中，殼聚糖作為天然的多醣類化合物，具有生物相容性好、可降解等特點(diǎn)，被廣泛應(yīng)用于制備溫敏凝膠。而甘油磷酸鈉則是一種陽離子表面活性劑，能夠與殼聚糖發(fā)生反應(yīng)，通過交聯(lián)形成溫敏凝膠。本研究旨在以殼聚糖與甘油磷酸鈉為原料，通過化學(xué)交聯(lián)法制備溫敏凝膠，并測試其熱敏性能和藥物緩釋特性。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