石杉碱甲分子印迹聚合物的制备及缓释特性

Preparation and sustained release characteristics of Huperzine A molecularly imprinted polymer

摘要:

石杉碱甲(Hup A)是从蛇足石杉中提取出来的可逆性乙酰胆碱酯酶抑制剂，对AD症具有良好的治疗效果。用分子印迹和沉淀聚合技术，以甲基丙烯酸为功能单体，乙二醇二甲基丙烯酸乙酯为交联剂成功制备石杉碱甲分子印迹聚合物（MIP）。通过傅里叶变换红外光谱，热重分析，扫描电子显微镜对印迹聚合物（MIP）进行了表征。通过静态吸附、动态吸附、体外释药和MTT等实验对MIP性能进行了评价。实验结果表明MIP对石杉碱甲存在特异性和非特异性两种结合位点。市售石杉碱甲片在1h内快速释放，累积释放率达90%以上，有明显的突释现象。而MIP在1h后释放平缓，在24h附近达到平衡，可以达到缓慢释放的效果。释放动力学符合Peppas模型，释放指数n=0.48，为非Fickian扩散机理。MIP生物相容性良好，L929小鼠成纤维细胞对MIP的细胞毒性数据显示，细胞存活率高于93%。

Abstract:

Huperzine A (Hup A)is as an acetylcholinesterase inhibitor used to treat Alzheimer's disease. We present a new the molecularly imprinted polymers( MIP), which can well control the release of Hup A. The MIP were prepared by precipitation polymerization using Hup A as template, methacrylic acid（MAA）as functional monomer, ethylene glycol dimethyl acrylate as the crosslinking agent. The synthesized MIP were characterized by SEM、TGA and FT-IR spectrometer. The performance of MIP was evaluated by static adsorption, dynamic adsorption, in vitro drug release and MTT. The results showed that MIP had specific and nonspecific binding sites to Hup A. Hup A tablets were rapidly released within 1 hour, and the cumulative release rate was more than 90%. MIP release gently after 1h and reach equilibrium near 24h, which can achieve the effect of slow release. The release kinetics conforms to the Peppas model and the release index is n = 0.48, which implies a non Fickian diffusion mechanism. The biocompatibility of MIP was good. The cytotoxicity data of L929 mouse fibroblasts to MIP showed that the cell survival rate was higher than 93%. were prepared by precipitation polymerization using Hup A as template, methacrylic acid（MAA）as functional monomer, ethylene glycol dimethyl acrylate as the crosslinking agent. The synthesized MIP were characterized by SEM、TGA and FT-IR spectrometer. The performance of MIP was evaluated by static adsorption, dynamic adsorption, in vitro drug release and MTT. The resμlts showed that MIP had specific and nonspecific binding sites to Hup A. Hup A tablets were rapidly released within 1 hour, and the cumulative release rate was more than 90%. MIP release gently after 1h and reach equilibrium near 24h, which can achieve the effect of slow release. The release kinetics conforms to the Peppas model, and the release index n = 0.48, which is a non Fickian diffusion mechanism. The biocompatibility of MIP was good. The cytotoxicity data of L929 mouse fibroblasts to MIP showed that the cell survival rate was higher than 93%.