Curcumin-polymeric nanoparticles against colon-26 tumor-bearing mice: cytotoxicity, pharmacokinetic and anticancer efficacy studies

Abstract

Context: Curcumin (CUR), can inhibit proliferation and induce apoptosis of tumor cells, its extreme insolubility and limited bioavailability restricted its clinical application.

Objective: An innovative polymeric nanoparticle of CUR has been developed to enhance the bioavailability and anti-cancer efficacy of CUR, in vitro and in vivo.

Materials and methods: Cationic copolymer Eudragit E 100 was selected as carrier, which can enhance properties of poor bioavailable chemotherapeutic drugs (CUR). The CUR-loaded Eudragit E 100 nanoparticles (CENPs) were prepared by emulsification-diffusion-evaporation method. The in vitro cytotoxicity study of CENPs was carried out using sulphorhodamine B assay. Pharmacokinetic and anti-cancer efficacy of CENPs was investigated in Wister rats as well as colon-26 tumor-bearing mice after oral administration.

Results: CENPs showed acceptable particle size and percent entrapment efficiency. In vitro cytotoxicity studies in terms of 50% cell growth inhibition values demonstrated ∼19-fold reduction when treated with CENPs as compared to pure CUR. ∼91-fold increase in Cmax and ∼95-fold increase in AUC0-12h were observed indicating a significant enhancement in the oral bioavailability of CUR when orally administered as CENPs compared to pure CUR. The in vivo anti-cancer study performed with CENPs showed a significant increase in efficacy compared with pure CUR, as observed by tumor volume, body weight and survival rate.

Conclusions: The results clearly indicate that the developed polymeric nanoparticles offer a great potential to improve bioavailability and anticancer efficacy of hydrophobic chemotherapeutic drug.

Keywords: Anti-cancer efficacy; bioavailability; colon-26 cells; cytotoxicity; polymeric nanoparticles.