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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 study the corneal adhesion, tear and aqueous humor pharmacokinetics of normal mycophenolate mofetil suspension and chitosan-modified mycophenolate mofetil suspension in rabbits. Methods: Nanosuspensions were prepared by film dispersion and high pressure homogenization, and chitosan modified nanosuspensions with adhesion and positive charge were further prepared by chitosan modification of nanoparticles. The content of mycophenolate mofetil and mycophenolic acid in corneal adhesion, lacrimal fluid and aqueous humor were detected by HPLC. Results: The suspension of eye drops showed beige creamy liquid. The drug particles of nanosuspension and chitosan modified nanosuspension were spherical and uniform in size. The average particle size of nanosuspension was 592 nm, polydisperse The coefficient of determination (Pdl) was 0.114 and the Zeta was -29.6 mV. The average particle size of chitosan modified nanosuspension was 442 nm, Pdl was 0.096 and Zeta was +45 mV. Compared with the conventional suspension eye drops, the nanosuspension corneal adhesion, tear and aqueous humor significantly increased drug concentration, and chitosan modified nano-suspension can further improve the corneal adhesion and tear , Aqueous humor drug concentration. CONCLUSIONS: Nano-suspensions can promote and enhance corneal adhesion and drug absorption after topical administration of mycophenolate mofetil, whereas modified nano-suspensions with chitosan can further promote and enhance corneal adhesion and absorption .