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

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免眼角膜粘附性、泪液和房水药物动力学特性。方法：以薄膜分散一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59213111，多分散系数（Pdl）为0．114，Zeta为-29．6mV，壳聚糖修饰型纳米混悬剂平均粒径442hill，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。

Preparation and Intraocular Pharmacokinetics in Rabbits of Novel Mycophenolate Mofetil Nanosuspension

Objective:To investigate the corneal mucoadhesion and the pharmacokinetic characteristics of mycophenolate mofetil nanosuspension and chitosan modified mycophenolate mofetil nanosuspension in tears and aqueous humor.Method:Mycophenolate mofetil nanosuspension and chitosan modified mycophenolate 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 concentratio...