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疏水性药物微胶囊的自组装构筑及其缓释性能研究
Research on Fabrication of Hydrophobic Drug Microencapsules by Layer-by-layer Assembly and Their Release Property
【作者】 陈幼芳;
【作者基本信息】 浙江大学 , 应用化学, 2006, 博士
【摘要】 逐层自组装方法(Layer-by-layer assembly)是一种重要的有机超薄膜制备技术,在药物缓释、生物传感器和膜分离等方面有重要应用。其中通过LbL方法交替组装构筑具有特殊功能的多层膜应用于药物缓释领域,近年来越来越受到人们的关注,具有重要的研究意义。 论文研究了聚苯乙烯磺酸钠(PSS)、壳聚糖(CHI)、聚(二烯丙基二甲基氯化铵)(PDDA)在约0.005-1.000mol/LNaCl水溶液或约3—60%乙醇水溶液中的粘度,PSS与PDDA在溶液中的线团尺寸随着NaCl浓度的增加而不断减小;当乙醇浓度分别为33.4%,20.2%和17.0%时,PSS、壳聚糖乳酸盐和PDDA三种聚电解质的特性粘数相应出现极大值(溶解最佳),它们的线团尺寸也较大。 论文研究了PSS/PDDA等聚电解质多层膜的构筑,比较系统地考察了不同组装条件下聚电解质多层膜的性质与形貌,用AFM、UV光谱、接触角测定等方法对多层膜的表面形貌、组装量、表面亲水性进行表征。结果表明,PSS/PDDA多层膜的组装量与聚电解质浓度呈非线性的递增关系,而且存在组装量的临界浓度现象;外加盐浓度与乙醇浓度也会对多层膜组装量产生较强的影响。认识了多层膜组装量、表面粗燥度等的变化规律。 论文研究了以PDDA、CHI、PSS、明胶、海藻酸钠、壳聚糖季铵盐(PDC)为聚电解质材料,层层组装构筑吲哚美辛、硝苯心定和青蒿素三种疏水性药物微胶囊。用Z电位法、SEM、TEM、CLSM等实验技术表征微胶囊的形貌、组装过程、释放过程和降解行为,探索组装条件与微胶囊缓释性能之间的关系。Z电位实验验证了PDDA和PSS在吲哚美辛晶体上的交替沉积。 论文研究了吲哚美辛、硝苯心定和青蒿素三种药物微胶囊的缓释性能。实验结果发现,在组装过程中药物晶体粒径、聚电解质层数、聚电解质的种类、聚电解质浓度等因素对微胶囊药物的缓释性能有影响,其中聚电解质材料、组装层数是控制缓释速度的关键因素。对于硝苯心定与青蒿素微胶囊缓释性能时发现囊壁中的PSS/明胶多层膜比PSS/PDDA膜更能够有效地控制硝苯心定的释放。(壳聚糖乳酸盐/明胶)4,6,8包覆的吲哚美辛缓释药物的释放速度随聚电解质层数的增加而成比例减慢。通过改变聚
【Abstract】 Layer-by-layer (LBL) assembly method with the advantage of versatility, simplicity and easy operation was widely applied, because the thickness, structure and function of films obtained were controllable. The study of microencapsulated drugs by using LBL technique was very active. Thus the basic research of LBL has received considerable interest.In this paper, the alternate assembly of poly (dimethyldiallyl ammonium chloride) (PDDA), poly (styrene sulfonate) (PSS), chitosan lactate (CHI), quaternary chitosan salt were studied. Influence of assembling condition on the properties of the multilayer membrane was investigated with ultraviolet spectrometer (UV), atom force microscope (AFM) and Contact Angle meter.Layer-by-layer self-assembled membranes of poly (styrene sulfonate) (PSS) and poly (dimethyldiallyl ammonium chloride) (PDDA) with a wide concentration range of polyelectrolytes were prepared at different concentrations of sodium chloride. The relation between ultraviolet (UV) absorbance of the self-assembled membrane and the solution concentrations of polyelectrolyte (Cp) and added salt (Cs) in the layer-by-layer processes was investigated. It was found that the UV absorbance (A) exhibited increasing, constant and decreasing trend with increasing CP respectively, which depended on added salt concentration; furthermore, most ACP curves displayed a discontinuous phenomenon, which was related to the critical concentration of the polyelectrolyte in solution. So the solution concentrations of polyelectrolyte (CP) and added salt (Cs) affected the assembed amount of polyelectrolyte in the membrane.Layer-by-layer self-assembled membranes of PDDA/PSS and CHI/PSS were prepared at different concentrations of added alcohol, that its concentration was expressed as Calcohol. The UV absorbance of according multilayer prepared from these solutions was also expressed as A. Each of the intrinsic viscosity ([η])Calcohol curve has maximum point, at the same time, each of the ACalcohol curve has minimum point. When Calcohol is same, the maximum point of [η ]Calcohol curve is near to the minimum one of ACaloohol curve.