Fabrication, characterization and optimization of artemether loaded PEGylated solid lipid nanoparticles for the treatment of lung cancer

Abstract

Lung cancer is one of the leading cancer killer in both men and women worldwide. Toxicity of anticancer drugs towards normal cells is one of the major concern impeding the effective chemotherapy. Artemether (ART), an anti-malarial agent, revealed cytotoxic effect on tumor cells by down-regulating the expression of matrix metalloproteinase (MMP)−9, hypoxia-inducible factor (HIF)−1a, VEGF and other related proteins. The present investigation demonstrates development of ART loaded solid lipid nanoparticles (ART-SLNs) for the treatment of lung cancer. A 23 full factorial design was applied to optimize ART-SLNs systematically. Concentration of drug, surfactant concentration and homogenization cycles were selected as an independent variables, and % drug loading (%DL), % entrapment efficiency (%EE) and particle size were selected as dependent variables. The mean diameter of optimized ART-SLNs was found to be 419 ± 09 nm, with %EE of 78.66 ± 1.93%, and %DL of 9.17 ± 0.11%. The in vitro dissolution studies revealed sustained drug release profile, revealing best fit with Korsmeyer-Peppas model. Further, the in vitro lipolysis study confirmed that ART-SLNs stabilized using MPEG2000-DSPE, exhibited anti-lipolytic effect. The stability (accelerated) studies does not showed any significant change in characteristics of developed ART-SLNs.