四乙酰芍药苷聚合物胶束的制备及其对大鼠脑缺血再灌注损伤的保护作用  

Preparation of Tetra-acetylated Paeoniflorin Polymeric Micelles and Their Protective Effects against Rat Cerebral Ischemia-reperfusion Injury

作　　者：张赟[1] 安佃云 沈腾[1] 王建新[1] 蒋晨[1] 

机构地区：[1]复旦大学药学院药剂学教研室,智能化递药教育部重点实验室,上海201203

出　　处：《中国医药工业杂志》2014年第11期1036-1041,共6页Chinese Journal of Pharmaceuticals

基　　金：国家自然科学基金面上项目(81072594)

摘　　要：以Pluronic P123为载体材料,采用固体分散-水化法制备包载四乙酰芍药苷(1)的聚合物胶束,以星点设计-效应面法优化处方。优化所得胶束包封率为97.4%、载药量为10.5%、平均粒径为20.5 nm;胶束中1溶解度是原药的585倍。采用线栓法建立大鼠局灶性脑缺血-再灌注(ischemia-reperfusion,I/R)损伤模型。聚合物胶束显著增加了1在I/R损伤大鼠脑内,特别是脑缺血侧的蓄积量,降低了40%的脑部梗死总面积,显著改善了脑损伤神经行为学评分。结果表明1聚合物胶束有效克服了芍药苷的生物药剂学缺陷和1注射液采用增溶剂的刺激性问题,取得预期对脑缺血再灌注损伤的神经保护作用。Tetra-acetylated paeoniflorin （1） loaded polymeric micelles were prepared by solid-dispersing and hydration method with Pluronic P 123 as the carrier.The formulation was optimized by central composite design-response surface method.The results showed that the entrapment efficiency and drug loading of the optimized micelles were 97.4％ and 10.5 ％ with the average diameter of 20.5 nm.Moreover,polymeric micelles increased the solubility of 1 to 585 times as against the bulk drug.Focal cerebral ischemia-reperfusion （I/R） injury model was induced by middle cerebral artery occlusion （MCAO） followed by reperfusion.In I/R injury model rats,polymeric micelles showed significant accumulation of 1 in the brain,especially in the ischemic hemisphere.Furthermore,1-loaded micelles significantly reduced infarct size by 40 ％ and ameliorated neurological deficit scores.In conclusion,1-loaded polymeric micelles succeed in preventing the biopharmaceutical disadvantage of paeoniflorin and the side effects of 1 injection using solubilizers,and exerting protective effects against cerebral ischemia-reperfusion injury.

关 键 词：四乙酰芍药苷 PLURONIC P123 聚合物胶束 溶解度 缺血再灌注损伤 

分 类 号：R944.9[医药卫生—药剂学]