Antitumor activity of gemcitabine hydrochloride loaded lipid polymer hybrid nanoparticles (LPHNs): In vitro and in vivo

Abstract

The present study demonstrated the application of gemcitabine hydrochloride (GEM) loaded lipid polymer hybrid nanoparticles (LPHNs) for the enhancement the chemotherapeutic response. GEM, which is an anti-tumor drug, is frequently utilized for the treatment of non-small cell lung cancer, breast cancer and pancreatic cancer. GEM loaded LPHNs were formed and examined for pharmacokinetic profile and in vivo anticancer activity. Modified double emulsion solvent evaporation method was employed in the preparation of the LPHNs. Cytotoxicities of the GEM loaded LPHNs formulation were evaluated on MCF-7 and MDA-MB-231 cells by MTT assays. Pharmacokinetics and in vivo anticancer efficacy studies were conducted following intraperitoneal administration in female Sprague-Dawley rats. In vivo pharmacokinetic studies in rats exhibited the advantage of the GEM loaded LPHNs over commercial product Gemko® and the GEM loaded LPHNs had longer circulation time. The half-life of GEM in LPHNs formulation was notable advanced (4.2 folds) comparing to commercial product of GEM (native). These findings indicated that GEM loaded LPHNs can be used for enhancing antitumor efficacy for breast cancer treatment.

Keywords: Anti-tumor activity; Cytotoxicity; Gemcitabine hydrochloride; Lipid polymer hybrid nanoparticles; Pharmacokinetics.