【作者】 吴祥根； 辛萌； 史伟云；

【Author】 WU Xiang-gen,XIN Meng,SHI Wei-yun (State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Qingdao,266071, China)

【机构】 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；

【摘要】 目的研究霉酚酸酯纳米混悬剂及经壳聚糖修饰的霉酚酸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、泪液和房水中的霉酚酸酯和霉酚酸的含量。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592nm,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442nm,多分散系数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霉酚酸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。更多还原

【Abstract】 OBJECTIVE To investigate the corneal mucoadhesion, the Pharmacokinetic characters in lacrimal fluid and aqueous humor of mycophenolate mofetil nanosuspensions and chitosan modified mycophenolate mofetil nanosuspension. METHODS Mycophenolate mofetil nanosuspensions and chitosan modified mycophenolate mofetil nanosuspension were prepared by thin-film method and high pressure homogenization. The cationic muscoadhesive nanosuspension was obtained by modified the nanosuspension with chitosan. The concentrations of mycophenolate mofetil and mycophenolic acid in corneal muscoadhesive samples, lacrimal fluid and aqueous humor samples were determined by HPLC. RESULTS Nanosuspension or chitosan modified nanosuspension was ecru and the drug particles were discrete and spherical with smooth surfaces. As to nanosuspension, the mean diameter was 592nm, the Pdl 0.114 and Zeta-29.6mV. The mean diameter of chitosan modified nanosuspension had characters was 442nm, the Pdl 0.096 and Zeta +45mV. The nanosuspension had a higher drug concentration in corneal muscoadhesive samples, lacrimal fluid and aqueous humor samples than ordinary mycophenolate mofetil suspensuion, but the chitosan modified nanosuspension had a much higher concentrations compared to nanosuspension. CONCLUSION The nanosuspension modified with chitosan can markedly increase the corneal muscoadhesive and drug absorption.更多还原