Development and Evaluation of Chitosan-Coated PLGA Nanoparticles of Canagliflozin for the Treatment of Hepatic Cancer

Abstract

Aim: The aim of the study was to develop, optimize and evaluate chitosan-coated Poly (Lactic-Co- Glycolic Acid) (PLGA) Nanoparticles (NPS) of Canagliflozin (CFZ) against the proliferation of liver cancer cells.Materials and Methods: The PLGA NPs and chitosan-coated PLGA NPs containing CFZ was optimized keeping CFZ:PLGA ratios and PVA levels as independent variables and mean Particle Size (PS), Polydispersity Index (PDI), Zeta Potential (ZP), and percent Entrapment Efficiency (EE) as the responses.Results: The optimized CFZ-PLGA-NPs had PS, PDI, ZP, and EE values of 159 nm, 0.149, -36.5 mV, 84.8%, respectively. The concentration of chitosan coating (0.25%) was found to be optimum providing a PS of 277±23 nm, PDI of 0.241±0.011, ZP of 57.2±0.67 mV, and EE of 80.5±1.78%. The electron microscope images, FTIR spectra, and DSC thermograms confirmed the identity of individual components and the amorphous nature of CFZ in the C-CFZ-PLGA-NPs. The in vitro CFZ release from C-CFZ-PLGA-NPs (80.9±1.2%) was significantly higher than that from CFZ dispersion (25.9±1.4%) when studied for 48 h. The cell viability assay demonstrated significant enhancement of cytotoxicity of C-CFZ-PLGA-NPs against HepG2 cells compared to pure CFZ treatments. The C-CFZ-PLGA-NPs were found to be stable when tested for storage stability at 4ºC for 90 days. PS, PDI, and ZP remained stable during the entire study period.Conclusion: C-CFZ-PLGA-NPs can be considered potential candidates for further studies in providing a commercially viable, stable, and effective system for the delivery of CFZ

Keywords: Canagliflozin; Chitosan; Cytotoxicity; HepG2 Cells; Liver Cancer; Nanoparticles