摘要
目的研究钙黄绿素脂质体的细胞转运及其入胞机制。方法用薄膜分散法制备钙黄绿素脂质体,比较钙黄绿素水溶液和脂质体的体外释放过程,研究脂质体包裹对钙黄绿素在A549细胞内蓄积、分布和入胞途径的影响。结果钙黄绿素脂质体具有良好的缓释作用,可释放长达1周。相对于钙黄绿素水溶液,脂质体包裹使被动跨膜的钙黄绿素通过大胞饮和网格蛋白(clathrin)介导的内吞途径入胞,大幅度提高钙黄绿素入胞量,主要分布于溶酶体内。结论小分子水溶性药物可以通过脂质体包裹改变入胞途径,提高入胞能力,影响胞内分布。该结论为研究载有水溶性药物脂质体的细胞递送过程,进一步合理设计脂质体处方提供参考和依据。
OBJECTIVE To investigate the cellular delivery of calcein-loaded liposomes and the endocytosis mechanism. METHODS Liposomes were prepared by film dispersion method. The in vitro release profiles of ealcein solution and calcein loaded liposomes were compared via dialysis method, and the effects of liposome encapsulation on the cellular accumulation, intracellular dis- tribution and uptake mechanism of calcein were investigated on A549 cells. RESULTS The in vitro release test showed sustained re- lease of calcein from liposomes, which lasted for 1 week. Liposomes significantly increased the amount of total and intracellular calcein （ P 〈 0. 01 ）, and calcein distributed mainly in the lysosomes and outside of the nucleus. The mechanism study showed that liposomes transferred calcein into cells mainly by macropinocytosis and clathrin-dependent endocytic pathway. CONCLUSION Liposome encapsulation can increase the amount of intracellular calcein by changing the endocytic pathway of calcein. Liposome encapsulation is a potential and feasible way for enhancing cellular delivery.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2014年第15期1321-1326,共6页
Chinese Pharmaceutical Journal
基金
国家自然科学基金资助项目(30873176)
浙江省自然科学基金资助项目(LQ12H30004)
浙江省医药卫生科技计划(2012KYA067)
