氯碘羟喹纳米粒的制备及其功能性评价

Preparation and the biological function evaluation of Clioquinol nanopartices

目的以聚乙二醇(PEG)-聚乳酸羟基乙酸共聚物(PLGA)为载体,制备氯碘羟喹(CQ)的纳米给药系统。方法通过PEG引发的开环聚合物制备两亲性聚合物PEG-PLGA,采用乳化溶剂蒸发法制备CQ-PEG-PLGA纳米粒给药系统,并计算其载药量和包封率。采用透射电镜和粒度分析仪表征载药纳米粒的粒度和形态。以Hela细胞为模型,结合MTT法评价纳米粒给药系统的细胞毒性。SD大鼠予尾静脉注射给药后,检测其药动学行为。结果载药纳米粒的粒径约200 nm,CQ的负载量和包封率均随着投药量的提高而增大,体外细胞培养表明其能有效降低CQ的细胞毒性,能延长药物在SD大鼠体内的滞留时间并提高生物利用度。结论所制备的纳米粒给药系统可以有效改善CQ的水溶性、降低细胞的毒性、延长药物在体内的滞留时间并提高生物利用度,有望开发为抗老年痴呆的缓释给药系统。

OBJECTIVE To prepare nanoformulations of Clioquinol （CQ） based on nanoparteiles （NPs） of amphiphilic polymer PEG - PLGA. METHODS Amphiphilic polymer PEG - PLGA was synthesized by polymerization initiated by polyethylene glycol （ mPEG - NH2 ）. PEG - PLGA/BDBDP NPs via emulsification and solvent evaporation method were prepared, and the drug loading and entrapment efficiency were calculated. Morphology observation of NPs was performed by TEM. The average size of NPs was tested by DLS. Using Hela cell as a model, the eytotoxicity of CQ and NPs was tested by MTT. Pharmaeokinetic study of CQ and NPs was performed in SD rats after caudal vein administration. RESULTS The NPs with size smaller than 200 nm could be prepared by PEG - PLGA. Both drug loading content and entrapment efficiency increased as the CQ feed increased. Compared with raw CQ, the cytotoxicity of drug - loaded NPs was significantly decreased as illustrated by in vitro cell culture experiment. The residence time and bioavailability of drug - loaded NPs was significantly improved. CONCLUSION PEG - PLGA NPs can increase the water solubility of CQ, and reduce its cytotoxicity, prolong the residence time and enhance the bioavailability, which can be used as a potential anti - AD approach.