Development of asolectin-based liposomal formulation for controlled and targeted delivery of erlotinib as a model drug for EGFR monotherapy.

Abstract

The present investigation was envisaged to develop liposomal formulation for efficacious and targeted delivery of epidermal growth factor receptor (EGFR) inhibitor (erlotinib) against pancreatic cancer. The marketed formulations bearing current EGFR inhibitors exhibit serious adverse effects including severe skin, hemolytic and gastrointestinal toxicity. To address the obstacles, we have developed the liposomal formulation, by ether injection method, comprising erlotinib, a tyrosine kinase EGFR inhibitor, proposed to be targeted through enhanced permeability and retention effect (EPR) effect against pancreatic cancer. On succeeding, the liposomes were characterized for various pharmaceutical attributes. The developed liposomes found to sustain a particle size of 121 ± 10.7 nm, whereas PDI of 0.22 ± 0.01 with the surface charge value of -33.7 ± 2.30 mV. The entrapment efficiency and drug loading were found to be 82.60 and 15.89 (%w/w), respectively. The hemolysis study suggested that the developed formulation was safer compared with native drug solution. The proof of concept for enhanced efficacy and decreased toxicity has been established through in vitro assays. The IC50 for free erlotinib and formulation was found to be 2.0 ± 0.3 µg/ml and 1.1 ± 0.1 µg/ml, respectively. The effectivity was evident by cellular uptake study and apoptosis, whereas cell cycle arrest study indicated that erlotinib arrests the G0/G1 phase of cell cycle. Further the erlotinib-asolectin liposomal formulation enhanced cytotoxicity in PANC-1 cells at relatively low dose, proving to be an alternative for current chemotherapeutics against pancreatic cancer.