Cyclodextrin modified erlotinib loaded PLGA nanoparticles for improved therapeutic efficacy against non-small cell lung cancer.

Abstract

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.

• Authors: Bhuvaneshwar Vaidya, Vineela Parvathaneni, Nishant S Kulkarni, Snehal K Shukla, Jenna K Damon, Apoorva Sarode, Dipti Kanabar, Jerome V Garcia, Samir Mitragotri, Aaron Muth, Vivek Gupta
• Journal: International journal of biological macromolecules (Int J Biol Macromol) Vol. 122 Pg. 338-347 (Feb 01 2019) ISSN: 1879-0003 [Electronic] Netherlands
• PMID: 30401652 (Publication Type: Journal Article)
• Copyright: Copyright © 2018. Published by Elsevier B.V.

Chemical References

• Cyclodextrins
• Drug Carriers
• Polylactic Acid-Polyglycolic Acid Copolymer
• Erlotinib Hydrochloride

Topics

• Apoptosis (drug effects)
• Autophagy (drug effects)
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cyclodextrins (chemistry)
• Drug Carriers (chemistry)
• Drug Liberation
• Erlotinib Hydrochloride (chemistry, pharmacology, therapeutic use)
• Humans
• Lung Neoplasms (drug therapy, pathology)
• Nanoparticles (chemistry)
• Particle Size
• Polylactic Acid-Polyglycolic Acid Copolymer (chemistry)