基于新型生物黏附药物载体—酯化多孔淀粉的普萘洛尔鼻腔黏膜给药系统分析-analysis of propranolol nasal mucosal drug delivery system based on novel bioadhesive drug carrier - esterified porous starch.docx

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基于新型生物黏附药物载体—酯化多孔淀粉的普萘洛尔鼻腔黏膜给药系统分析-analysis of propranolol nasal mucosal drug delivery system based on novel bioadhesive drug carrier - esterified porous starch.docx

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基于新型生物黏附药物载体—酯化多孔淀粉的普萘洛尔鼻腔黏膜给药系统分析-analysis of propranolol nasal mucosal drug delivery system based on novel bioadhesive drug carrier - esterified porous starch

缩略语表英文缩写SAMSA英文全称S-Acetylmercaptosuccinicanhydride中文全称S-乙酰巯基丁二酸酐PSPorousstarch多孔淀粉PROPropranolol盐酸普萘洛尔PGMGastricmucinfromporcine猪胃黏蛋白NDDSNasaldrugdeliverysystem鼻腔给药系统DSDegreeofSubstitution取代度IRInfraredspectroscopy红外光谱仪XRDX-raydiffractionX射线衍射法SEMScanningelectronmicroscopy扫描电子显微镜UVUltravioletspectroscopy紫外分光光度计DSCDifferentialscanningcalorimeter差示扫描量热仪MTRMucociliarytransportrate黏膜输送速率Novelbioadhesivematerial-studyonthenasaladmini-strationofpropranolol-carryingS-AcetylmercaptosuccinicporousstarchmicrosphereAbstractAsweknow,porousstarch(PS)isanovelmodifiedstarchwhichhasabundantmicro-sizedporesfromthesurfaceofstarchgranulesextendingtothecenter.Porousstarchhasalargerelativesurfaceareas.Ithasbeenwidelyusedasanadsorbentinthefieldofmedicine,food,agricultureandothersduetoitslargespecificsurfaceareaandadsorptioncapacity.Therefore,themicroporousstarchcanbeusedasanexcellentdrugcarriertoabsorbdrugs.However,duetoitspoormucoadhesiveability,naturalporousstarchcouldberapidlyclearedbytherespiratorysystem,resultinglowbioavailabilityofdrugs.Toovercometheseshortcomings,modifiedporousstarchhasbeendevelopedtoprolongtheresidencetimeofthenasaldrug.Previousresearchresultshavebeenshownthatdisulphidebondsbetweenthiolatedpolymersandcysteine-richsubdomainsofmucusglycoproteinscouldenhancemucoadhesivepropertiesofthiomers.Inthisstudy,tofurtherimproveitsmucoadhesivecharacteristics,porousstarchwasmodifiedthroughesterificationusingS-Acetylmercaptosuccinicanhydride(SAMSA).TheaimofourstudywastosynthesizeandevaluatethenewmucoadhesivematerialsofS-Acetylmercaptosuccinicporousstarch(SAMSA-PS),toselectepropranolol(PRO)asmodeldrugtoprepareSAMSA-porousstarch-PROmucoadhesivemicrospheres,andtostudyitsmucoadhesiveproperties,drugloadingandreleasecharacteristics.Besides,theciliotoxicitieswasalsoevaluated.MethodsSynthesisofS-Acetylmercaptosuccinicporousstarch(SAMSA-PS)anditscharacterizationSAMSA-porousstarchwaspreparedbyesterificationofporousstarchwithS-Acetylmercaptosuccinicanhydride.Bytheorthogonaldesigns，thefactor