Targeted delivery of monoclonal antibody conjugated docetaxel loaded PLGA nanoparticles into EGFR overexpressed lung tumour cells

Abstract

The aim of this study was to develop anti-EGFR antibody conjugated poly(lactide-co-glycolide) nanoparticles (NPs) to target epidermal growth factor receptor, highly expressed on non-small cell lung cancer cells to improve cytotoxicity and site specificity. Cetuximab was conjugated to docetaxel (DTX) loaded PLGA NPs by known EDC/NHS chemistry and characterised for size, zeta potential, conjugation efficiency and the results were 128.4 ± 3.6 nm, –31.0 ± 0.8 mV, and 39.77 ± 3.4%, respectively. In vitro release study demonstrated sustained release of drug from NPs with 25% release at pH 5.5 after 48 h. In vitro cytotoxicity studies demonstrated higher anti-proliferative activity of NPs than unconjugated NPs. Cell cycle analysis and apoptosis study were performed to evaluate extent of cell arrest at different phases and apoptotic potential for the formulations, respectively. In vivo efficacy study showed significant reduction in tumour growth and so antibody conjugated NPs present a promising active targeting carrier for tumour selective therapeutic treatment.

Keywords:

• Antibody
• epidermal growth factor receptor
• docetaxel
• cetuximab
• poly(lactide-co-glycolide)

Acknowledgements

The authors acknowledge the Zydus Research Center, Ahmedabad and Center of Relevance and Excellence in NDDS, TIFAC at Faculty of Pharmacy, The M.S. University of Baroda for providing the research facilities to the team.

Disclosure statement

No potential conflict of interest was reported by the authors.