【摘要】 目的　选择不同亲水性及空间构型的添加剂,研究其对聚乳酸聚乙烯醇酸共聚物(polylactic co glycolicacid, PLGA)药物释放动力学的影响,为心血管药物局部用药控释制剂的研究提供理论依据。方法　用抗细胞增生药物2 氨基色酮(U 86)作为代表性药物,用溶剂浇铸和压膜结合的方法制备药物/PLGA/添加剂双层膜,在37℃磷酸缓冲液中测定体外药物释放并用扫描电镜观察表面形态。结果　水溶性添加剂明显地提高了U- 86的释放率,并转变为近似的单阶段模式。药物释放速率与基质的失重速率非常吻合。水溶性添加剂的基质在水中形成高度多孔的结构。结论　添加剂的水溶性、分子量大小及空间构型等对于聚合物基质的孔隙结构具有决定性作用,而这些孔隙结构的特征又影响着药物释放机制以及释放动力学模式。更多还原

【Abstract】 Aim To evaluate the effects of an array of additives on drug release from double-layered poly(lactic-co-glycolic acid) (PLGA) matrices. Methods Additives differing in molecular size, hydrophilicity and steric configuration were selected for this study. An anti-proliferative 2-aminochromone, U-86983 (U-86, Pharmacia and Upjohn), was used as a model agent because of our interest in investigating local drug delivery systems for the inhibition of restenosis. Results In vitro release of U-86 from PLGA matrices without additive showed a typical biphasic release kinetics, i.e. a slow diffusion release (Phase I) followed by a fast erosion-mediated release (Phase II). The water-soluble additives in PLGA matrices changed the biphasic release pattern to a near monophasic profile by increasing the release rate of the Phase I. Increasing the ratio of additives to PLGA in matrices caused a significant increase in the U-86 release rates. A high molecular weight water-soluble additive, Pluronic F127, resulted in a matrix showing perfect zero-order release kinetics. The morphologic evaluation of matrices using scanning electron microscopy indicated that the water-soluble additives were leachable and thus generated a highly porous structure in the matrices. Conclusion Water-solubility, molecular size and steric configuration of the additives are the important determinants in generating various types of pore structures in polymer matrix which in turn affect the release mechanism and release kinetics.更多还原