Lipid Nanocapsules for Imatinib Delivery: Design, Optimization and Evaluation of Anticancer Activity Against Melanoma Cell Line.

Abstract

Lipid nanocapsules (LNCs) represent a stable, biocompatible and worthwhile drug delivery system, demonstrating significant potential as gene/drug delivery platforms for cancer therapy. Imatinib, a potent tyrosine kinase inhibitor, has revolutionized the therapy of malignancies resulting from abnormal tyrosine kinase activity. However, its Clinical effectiveness in cancer treatment is hampered by its off-target side effects. In this study, we have investigated the potential benefits of LNCs as a novel drug delivery vehicle for imatinib with a view to improve drug efficacy. LNC formulations were prepared by phase-inversion temperature method and the effects of various formulation variables were assessed using full factorial design. The cytotoxicity and cellular uptake of optimized formulation were investigated against B16F10 melanoma cell line. Analysis of result by Design-Expert® software indicated that Solutol HS15 percent was the most effective parameter on the encapsulation efficiency, particle size, zeta potential, and release efficiency of LNCs. The optimized formulation revealed a particle size of 38.96 ± 0.84 nm, encapsulation efficiency of 99.17 ± 0.086%, zeta potential of -21.5 ± 0.61 mV, release efficiency of 60.03 ± 4.29, and polydispersity index of 0.24 ± 0.02. The imatinib loaded LNCs showed no hemolysis activity. Fluorescent microscopy test showed that the cellular uptake of LNCs was time dependent and density of fluorescent signals increased with time in cells. The in-vitro cytotoxicity study indicated that imatinib kept its pharmacological activity when loaded into LNCs. These results introduced imatinib loaded LNCs as a promising candidate for further investigation in cancer therapy.