Improved pharmacokinetics and reduced side effects of doxorubicin therapy by liposomal co-encapsulation with curcumin.

Abstract

The goal of the current study was to investigate the pharmacokinetic profile, tissue distribution and adverse effects of long-circulation liposomes (LCL) with curcumin (CURC) and doxorubicin (DOX), in order to provide further evidence for previously demonstrated enhanced antitumor efficacy in colon cancer models. The pharmacokinetic studies were carried out in healthy rats, following the i.v. injection of a single dose of LCL-CURC-DOX (1\u2009mg/kg DOX). For the tissue distribution study, DOX concentration in tumors, heart and liver were measured after the administration of two i.v. doses of LCL-CURC-DOX (2.5\u2009mg/kg DOX and 5\u2009mg/kg CURC) to Balb/c mice bearing C26 colon tumors. Markers of murine cardiac and hepatic oxidative status were determined to provide additional insights into the benefit of co-encapsulating CURC and DOX in LCL over DOX-induced adverse effects in these organs. The current study demonstrated that the liposomal association of CURC and DOX effectively improved the pharmacokinetics and biodistribution of DOX, limiting its side effects, via CURC-dependent antioxidant effects.