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本文旨在探讨麦胚凝集素(wheat germ agglutinins,WGA)修饰的脂质体作为眼部药物递送载体的可行性。采用成膜水化法制备包载5-羧基荧光素(5-carboxyfluorescein,FAM)的脂质体(liposome loaded with FAM,LS/FAM),将巯基化的WGA经聚乙二醇桥联修饰于该脂质体表面(WGA-modified liposome loaded with FAM,WGA-LS/FAM)。测定WGA的巯基化程度,考察其修饰到脂质体表面后的生物活性,并对WGA-LS/FAM的理化性质和眼部生物黏附性能进行表征和评价。所得巯基化WGA每分子中含1.32个巯基。WGA-LS/FAM的平均粒径为(97.40±1.39)nm,多分散系数为0.23±0.01,FAM的包封率为(2.95±0.21)%,体外24 h的渗漏率约为4%。红细胞凝集实验表明,修饰到脂质体表面的WGA仍保持其糖蛋白结合活性。脂质体在大鼠眼部的消除过程符合一级动力学特征,WGA-LS/FAM的消除速率显著低于未经修饰的脂质体,表现出适合眼部给药的生物黏附特性。
This article aims to investigate the feasibility of using wheat germ agglutinins (WGA) modified liposomes as ophthalmic drug delivery vehicles. The liposome loaded with FAM (LS / FAM) was prepared by the membrane hydration method. The thiolated WGA was modified by polyethylene glycol The WGA-modified liposome loaded with FAM (WGA-LS / FAM). The degree of thiolation of WGA was determined, and the biological activity of WGA was evaluated. The physicochemical properties and ocular bioadhesion of WGA-LS / FAM were characterized and evaluated. The resulting thiolated WGA contains 1.32 mercapto groups per molecule. The mean particle size of WGA-LS / FAM was (97.40 ± 1.39) nm, the polydispersity was 0.23 ± 0.01. The entrapment efficiency of FGA was (2.95 ± 0.21)% and the leak rate was about 4% in vitro. Erythrocyte agglutination experiments showed that WGA modified to the liposome surface still retained its glycoprotein binding activity. The elimination of liposomes in the rat eye was in accordance with the first-order kinetic characteristics. The elimination rate of WGA-LS / FAM was significantly lower than that of the unmodified liposomes and showed the bioadhesive properties suitable for ophthalmic administration.