姜黄素介孔缓释载药系统制备工艺优化及其体外抗肿瘤活性研究

Optimization of the preparation of curcumin mesoporous sustained-release drug loading system and its in vitro antitumor activity

目的制备姜黄素纳米介孔缓释载药系统并对其制备工艺进行优化,评价载药系统的相关表征及缓释性能。方法采用动态吸附法制备姜黄素纳米介孔缓释载药系统,以载药率和包封率作为评价指标,以正交设计优化处方及工艺。通过扫描电镜、透射电镜、粒径等方法进行表征。最后对姜黄素纳米介孔载药系统的溶解度与累积溶出率进行考察。以MTT法考察姜黄素和姜黄素纳米介孔载药系统对A549细胞和MCF-7细胞的体外细胞毒性。使用Dil和Hoechst-33258染色A549细胞,考察细胞摄取能力。结果最优制备工艺:药物载体-投料比为5∶1,载药温度为30℃,溶剂为80%乙醇。此条件下制备的载药系统载药量为78.17%,包封率为98.23%。体外溶出实验结果表明姜黄素纳米介孔载药系统在一定时间内具有缓释作用。姜黄素纳米介孔载药系统不仅对A549和MCF-7细胞的抑制率均高于姜黄素,而且还具有更优异的摄取能力。结论所制备的姜黄素纳米介孔缓释载药系统具有较高的包封率和载药量,相较于游离姜黄素具有更高的溶解度、体外溶出、体外细胞毒性和摄取能力。

Objective To optimize the preparation of curcumin nano-mesoporous sustained release drug delivery system and evaluate the relevant characterization and sustained release performance of the system.Methods The curcumin nano-mesoporous drug loading system was prepared by dynamic adsorption method,the drug loading rate and encapsulation rate were used as evaluation indicators,and the prescription and process were optimized by factor orthogonal design.Characterization was conducted by methods such as scanning electron microscopy,transmission electron microscopy,and particle size.Finally,the solubility and cumulative dissolution rate of curcumin nano-mesoporous drug carrier system were determined.The in vitro cytotoxicity of curcumin and curcumin nano mesoporous drug loading system on A549 cells and MCF-7 cells was investigated by MTT.A549 cells were stained using Dil and Hoechst-33258 to determine cell uptake capacity.Results The optimized preparation was as follows:the drug carrier-feeding ratio was 5∶1,the temperature was 30℃,and the solvent was 80%ethanol.The curcumin nano-mesoporous drug loading system prepared under this condition had an average drug loading of 78.17%and an average encapsulation rate of 98.23%.The in vitro dissolution showed that the curcumin nano-porous drug delivery system had a sustained release effect within certain time.The curcumin nano-mesoporous drug loading system not only had a higher inhibition rate on A549 and MCF-7 cells than the curcumin group but also a better uptake ability.Conclusion The curcumin nano-mesoporous sustained-release drug loading system has a high encapsulation rate and drug loading,and it has better solubility,in vitro dissolution,in vitro cytotoxicity,and uptake ability than free curcumin.