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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 nano-drug delivery system for chloroquine (CQ) by using polyethylene glycol (PEG) -polylactic acid glycolic acid copolymer (PLGA) as carrier. Methods PEG-PLGA, an amphiphilic polymer, was prepared by ring-opening polymerization initiated by PEG. CQ-PEG-PLGA nanoparticle drug delivery system was prepared by emulsion solvent evaporation. The drug loading and entrapment efficiency were calculated. The particle size and morphology of drug-loaded nanoparticles were characterized by transmission electron microscopy and particle size analyzer. Hela cells as a model, combined with MTT method to evaluate the cytotoxicity of the nanoparticle drug delivery system. Sprague-Dawley rats were injected into tail vein to test their pharmacokinetics. Results The particle size of drug-loaded nanoparticles was about 200 nm. The loading and encapsulation efficiency of CQ increased with the increase of dosage. In vitro cell culture showed that it could effectively reduce the cytotoxicity of CQ, Dwell time in vivo and improve bioavailability. Conclusion The prepared nanoparticle drug delivery system can effectively improve the water solubility of CQ, reduce the toxicity of cells, prolong the drug residence time in vivo and increase the bioavailability, and is expected to be developed as a sustained release drug delivery system for anti-Alzheimer’s disease.