Optimization of the process parameters for the fabrication of a polymer coated layered double hydroxide-methotrexate nanohybrid for the possible treatment of osteosarcoma

Abstract

The optimization is reported of various process parameters for the development of poly(lactic-co-glycolic acid, PLGA) coating on Mg–Al layered double hydroxide (LDH) nanoparticles intercalated with the anticancer drug methotrexate (MTX). Both double and single emulsion-solvent evaporation techniques were adapted to synthesize the PLGA coated, MTX drug loaded nanoparticles as above, with and without LDH. While keeping some of the process parameters constant, the homogenization speed, concentration of PLGA, LDH-MTX, MTX and surfactants, aqueous and organic phase volume involved in the synthesis of the PLGA-MTX and PLGA-LDH-MTX nanoparticles, were varied and evaluated to obtain the desired particle size range and drug entrapment efficiency for specific use. The optimized and a few selected unoptimized nanoparticles were further assessed for in vitro drug release kinetics and time and dose dependent in vitro cell viability bioassay, in vitro MTX uptake study using human osteosarcoma, MG-63 cell line. The in vivo pharmacokinetic study demonstrated the much higher therapeutic efficacy of the optimized PLGA-LDH-MTX and PLGA-MTX nanoparticles in terms of the enhanced half life of the drug and the slow clearance rate compared to those of the bare MTX drug.