Sun Mingshuang, Gao Yunyun, Zhu Zhihong, Wang Huixin, Han Cuiyan, Yang Xinggang, Pan Weisan
Shenyang Pharmaceutical University, No.103, Wenhua Road, Shenyang 110016, China.
Qiqihar Medical University, No. 333, Bukuibei Road, Qiqihar 161000, China.
Asian J Pharm Sci. 2017 Jan;12(1):51-58. doi: 10.1016/j.ajps.2016.07.007. Epub 2016 Aug 4.
The aim of the present study was to develop a poly-arginine modified nanostructured lipid carrier (R-NLC) by fusion-emulsification method and to test its pharmaceutical characteristics. The influence of R-NLC on A549 cells like cellular uptake and cytotoxicity was also appraised using unmodified NLC as the controlled group. As the results revealed, R-NLC had an average diameter of about 40 nm and a positive zeta potential of about +17 mv, the entrapment efficiency decreased apparently, and no significant difference on the drug release was found after R8-modification. The cellular uptake and cytotoxicity increased obviously compared with unmodified NLC. The cellular uptake mechanisms of R-NLC involved energy, macropinocytosis, clathrin-mediated endocytosis, and caveolin-mediated endocytosis. The outcomes of the present study strongly support the theory that cell penetrating peptides have the ability of enhancing the cellular uptake of nanocarriers.
本研究的目的是通过融合乳化法制备聚精氨酸修饰的纳米结构脂质载体（R-NLC），并测试其药学特性。以未修饰的NLC作为对照组，评估R-NLC对A549细胞的细胞摄取和细胞毒性等影响。结果显示，R-NLC的平均直径约为40 nm，zeta电位约为+17 mV，包封率明显降低，R8修饰后药物释放无显著差异。与未修饰的NLC相比，细胞摄取和细胞毒性明显增加。R-NLC的细胞摄取机制涉及能量、巨胞饮作用、网格蛋白介导的内吞作用和小窝蛋白介导的内吞作用。本研究结果有力地支持了细胞穿透肽具有增强纳米载体细胞摄取能力的理论。
