埃罗替尼
细胞凋亡
PLGA公司
化学
肺癌
药理学
纳米颗粒
体外
流式细胞术
盐酸厄洛替尼
癌症研究
材料科学
纳米技术
医学
免疫学
肿瘤科
表皮生长因子受体
生物化学
受体
作者
Bhuvaneshwar Vaidya,Vineela Parvathaneni,Nishant S. Kulkarni,Snehal K. Shukla,Jenna K. Damon,Apoorva Sarode,Dipti Kanabar,Jerome Garcia,Samir Mitragotri,Aaron Muth,Vivek Gupta
标识
DOI:10.1016/j.ijbiomac.2018.10.181
摘要
This study was aimed at developing a nanoparticle strategy to overcome acquired resistance against erlotinib in non-small cell lung cancer (NSCLC). To load erlotinib on biodegradable PLGA nanoparticles, erlotinib-cyclodextrin (Erlo-CD) complex was prepared using β-cyclodextrin sulfobutyl ether, which was in turn loaded in the core of PLGA nanoparticles using multiple emulsion solvent evaporation. Nanoparticles were characterized for size distribution, entrapment and loading efficiency, in-vitro release, and therapeutic efficacy against different lung cancer cells. Effect of formulation on cell cycle, apoptosis, and other markers was evaluated using flow cytometry and western blotting studies. The efficacy of optimized nanoformulation was evaluated using a clinically relevant in-vitro 3D-spheroid model. Results showed that Erlo-CD loaded nanoparticles (210 ± 8 nm in size) demonstrated 3-fold higher entrapment (61.5 ± 3.2% vs 21.9 ± 3.7% of plain erlotinib loaded nanoparticles) with ~5% loading efficiency and sustained release characteristics. Developed nanoparticles demonstrated significantly improved therapeutic efficacy against NSCLC cells in terms of low IC50 values and suppressed colony forming ability of cancer cells, increased apoptosis, and autophagy inhibition. Interestingly, 3D spheroid study demonstrated better anticancer activity of Erlo-CD nanoparticles compared to plain erlotinib. Present study has shown a premise to improve therapeutic efficacy against erlotinib-resistant lung cancer using modified nanoErlo formulations.
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