Zhang Jinxie, Tao Wei, Chen Yuhan, Chang Danfeng, Wang Teng, Zhang Xudong, Mei Lin, Zeng Xiaowei, Huang Laiqiang
School of Life Sciences, Tsinghua University, Beijing, 100084, People's Republic of China.
J Mater Sci Mater Med. 2015 Apr;26(4):165. doi: 10.1007/s10856-015-5498-z. Epub 2015 Mar 20.
A doxorubicin-loaded mannitol-functionalized poly(lactide-co-glycolide)-b-D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles (DOX-loaded M-PLGA-b-TPGS NPs) were prepared by a modified nanoprecipitation method. The NPs were characterized by the particle size, surface morphology, particle stability, in vitro drug release and cellular uptake efficiency. The NPs were near-spherical with narrow size distribution. The size of M-PLGA-b-TPGS NPs was ~110.9 nm (much smaller than ~143.7 nm of PLGA NPs) and the zeta potential was -35.8 mV (higher than -42.6 mV of PLGA NPs). The NPs exhibited a good redispersion since the particle size and surface charge hardly changed during 3-month storage period. In the release medium (phosphate buffer solution vs. fetal bovine serum), the cumulative drug release of DOX-loaded M-PLGA-b-TPGS, PLGA-b-TPGS, and PLGA NPs were 76.41 versus 83.11 %, 58.94 versus 73.44 % and 45.14 versus 53.12 %, respectively. Compared with PLGA-b-TPGS NPs and PLGA NPs, the M-PLGA-b-TPGS NPs possessed the highest cellular uptake efficiency in A549 and H1975 cells (lung cancer cells). Ultimately, both in vitro and in vivo antitumor activities were evaluated. The results showed that M-PLGA-b-TPGS NPs could achieve a significantly higher level of cytotoxicity in cancer cells and a better antitumor efficiency on xenograft BALB/c nude mice tumor model than free DOX. In conclusion, the DOX-loaded M-PLGA-b-TPGS could be used as a potential DOX-loaded nanoformulation in lung cancer chemotherapy.
采用改进的纳米沉淀法制备了载有多柔比星的甘露醇功能化聚（丙交酯 - 乙交酯）-b-D-α-生育酚聚乙二醇1000琥珀酸酯纳米粒（载多柔比星的M-PLGA-b-TPGS NPs）。通过粒径、表面形态、颗粒稳定性、体外药物释放和细胞摄取效率对纳米粒进行了表征。纳米粒呈近球形，粒径分布窄。M-PLGA-b-TPGS NPs的粒径约为110.9 nm（远小于PLGA NPs的约143.7 nm），zeta电位为-35.8 mV（高于PLGA NPs的-42.6 mV）。纳米粒在3个月的储存期内粒径和表面电荷几乎不变，表现出良好的再分散性。在释放介质（磷酸盐缓冲溶液与胎牛血清）中，载多柔比星的M-PLGA-b-TPGS、PLGA-b-TPGS和PLGA NPs的累积药物释放率分别为76.41%对83.11%、58.94%对73.44%和45.14%对53.12%。与PLGA-b-TPGS NPs和PLGA NPs相比，M-PLGA-b-TPGS NPs在A549和H1975细胞（肺癌细胞）中具有最高的细胞摄取效率。最终，评估了体外和体内抗肿瘤活性。结果表明，与游离多柔比星相比，M-PLGA-b-TPGS NPs在癌细胞中可实现显著更高水平的细胞毒性，对异种移植BALB/c裸鼠肿瘤模型具有更好的抗肿瘤效果。总之，载多柔比星的M-PLGA-b-TPGS可作为肺癌化疗中潜在的载多柔比星纳米制剂。
