聚氨基酸复合微胶囊对Hb的控制释放

Composite microcapsules of poly amino acids for Hb controlled release

以生物相容性好、价格低廉的海藻酸钠(ALG)为聚阴离子芯材,通过静电液滴装置制备了平均粒径在290μm左右、球形度好、表面光洁的海藻酸钙胶珠;再将生物可降解、具有介入治疗作用的聚精氨酸(PLA)与聚组氨酸(PLH)的混合物作为聚阳离子壁材,在海藻酸钙胶珠表面覆上一层高分子聚合膜以制备聚氨基酸复合微胶囊;并以牛血红蛋白Hb为药物模型,对微胶囊的控制释放性能进行了考察并将其初步应用于体外模拟口服给药。结果表明:聚氨基酸复合微胶囊在前0.5 h的累积释放量均低于40%,溶出结束时累积释放量均达到80%以上;ALG/(PLA-PLH)复合微胶囊和ALG/PLH微胶囊的药物释放速率均低于ALG/PLA微胶囊;于10 min成膜时间内制备的微胶囊具有较高的载药量、包封率和缓释性能;以pH 4.6 HAc-NaAc缓冲液为成膜溶媒制备的微胶囊,Hb持续释放时间和残留量均高于蒸馏水组;前2 h在模拟胃液的pH 1.2 HCl溶媒中累计释放的Hb不超过10%且绝大部分是在模拟肠液环境即pH 6.8 PBS溶媒中释放的;壳聚糖的引入能在一定程度上延长药物释放时间。聚氨基酸复合微胶囊具备一定的缓释性、pH响应性和生理黏附性,有望成为一种口服给药系统用药物载体。

The spheral and smooth calcium alginate beads whose average size was around 290 μm were obtained through the electronic droplet generator. With poly-L-arginine and poly-L-histidine, the novel ALG/（PLA- PLH） composite microcapsules were prepared by incubating the beads into the mixed solution of PLA and PLH for the polymeric membrane forming. In vitro release characteristics of the microcapsules were investigated and the feasibility of application as an oral protein delivery carrier was evaluated by choosing Hb as the protein-drug model. The results show that during the first half hour, the cumulative amount of Hb release from the composite microcapsules is lower than 40% and then reaches more than 80% in the end. The ALG/（PLA- PLH） group and the ALG/PLH group possesses a slower release rate compared with the ALG/PLA group. Due to the highest drug - loading and encapsulation ratio, the 10 rain group is considered as the optimal one. The microcapsules made from the pH 4.6 HAc - NaAc buffer has an obvious capacity of longtime release and low amount of leftover compared with the ones made from distilled water. The cumulative release of Hb is less than 10% when the microcapsules are immersed in the pH1. 2 HCl at the end of the first two hours, while most Hb is released in the pH 6.8 PBS buffer. The release time could be prolonged to some extent through the introduction of chitosan. The composite mierocapsules of poly amino acids are likely to become a potential carrier of oral drug delivery system due to their excellent performance.