吗替麦考酚酯纳米混悬剂的制备及其在兔眼内药动学研究  

Preparation and Intraocular Pharmacokinetics in Rabbits of Novel Mycophenolate Mofetil Nanosuspension

作　　者：姜皓然[1] 辛萌[1] 杨丽娜[1] 吴祥根[1] 

机构地区：[1]山东省眼科研究所山东省眼科学重点实验室-省部共建国家重点实验室培育基地,山东青岛266071

出　　处：《中国药师》2011年第5期615-620,共6页China Pharmacist

摘　　要：目的:研究普通吗替麦考酚酯纳米混悬剂及经壳聚糖修饰的吗替麦考酚酯纳米混悬剂在兔眼角膜粘附性、泪液和房水药物动力学特性。方法:以薄膜分散-高压乳匀法制备纳米混悬剂,并进一步选用壳聚糖修饰纳米药物粒子制得具有粘附作用、带正电荷的壳聚糖修饰型纳米混悬剂。HPLC法检测角膜粘附、泪液和房水中的吗替麦考酚酯和霉酚酸的含量。结果:混悬剂滴眼液呈米黄色乳液状,纳米混悬剂和壳聚糖修饰型纳米混悬剂药物粒子呈圆球状,粒径均一,纳米混悬剂平均粒径592 nm,多分散系数(Pdl)为0.114,Zeta为-29.6 mV,壳聚糖修饰型纳米混悬剂平均粒径442 nm,Pdl为0.096,Zeta为+45mV。与普通混悬剂滴眼液相比,纳米混悬剂的角膜粘附性、泪液和房水中药物浓度明显提高,而壳聚糖修饰型纳米混悬剂则可进一步提高角膜粘附性和泪液、房水中药物浓度。结论:纳米混悬剂可以促进和提高吗替麦考酚酯眼局部给药后角膜粘附和药物吸收,而壳聚糖修饰型纳米混悬剂可进一步促进和提高药物的角膜粘附和吸收。Objective： To investigate the corneal mucoadhesion and the pharmaeokinetic characteristics of mycophenolate mofetil nanosuspension and ehitosan modified mycophenolate mofetil nanosuspeusion in tears and aqueous humor. Method： Mycophenolate mofetil nanosuspension and chitosan modified mycophenolatc mofetil nanosuspension were prepared by thin-film method combined with high pressure homogenization. The cationic mucoadhesive nanosuspension was obtained by modified the nanosuspension with chitosan. The concentrations of mycophenolate mofetil and mycophenolic acid in corneal mucoadhesive samples, tears and aqueous humor samples were determined hy HPLC. Result： Nanosuspension and chitosan modified nanosuspension were both biege and the drug particles were uniform and spherical with smooth surfaces. As to nanosuspension, the mean diameter was 592 nm with Pdl of 0. 114 and Zeta potential of - 29. 6 inV. The above indices of the chitosan modified nanosuspension was 442 nm ,0. 096 and ＋ 45 mV, respectively. The nanosuspension showed higher drug concentrations in corneal mucoadhesive samples,tears and aqueous humor samples than ordinary mycophenolate mofetil suspensuion,while the chitosan modified nanosuspension had much higher concentrations compared with the nanosuspension. Conclusion： The nanosuspension modified with chitosan can markedly increase the corneal mucoadhesion and drug absorption.

关 键 词：吗替麦考酚酯 霉酚酸 纳米混悬剂 壳聚糖 

分 类 号：R945[医药卫生—微生物与生化药学]