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-circulating 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 mg/kg DOX). For the tissue distribution study, DOX concentration in tumours, heart and liver were measured after the administration of two i.v. doses of LCL-CURC-DOX (2.5 mg/kg DOX and 5 mg/kg CURC) to Balb/c mice bearing C26 colon tumours. 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.

Keywords:

• Liposomes
• curcumin
• doxorubicin
• pharmacokinetics
• biodistribution

Authors’ contributions

Study concept and design: A.P., A.S. and D.M.; Funding acquisition and project administration was done by A.P.; Liposomes preparation was performed by L.T. and B.S.; Acquisition of pharmacokinetic and biodistribution data was done by D.M., B.A., L.V.; In vivo studies and oxidative stress assays were performed by A.S., E.L., L.P., L.L. and V.R.; Analysis and interpretation of data was carried out by A.S., D.M., L.V, M.B. and A.P; Writing was done by A.S.; Drafting of manuscript was done by A.S. and A.P.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability

The data that support the findings of this study are available from the corresponding author upon request.

Additional information

Funding

This work was supported by a grant of the Romanian National Authority for Scientific Research and Innovation, CNCS-UEFISCDI, project number PN-II-RU-TE-2014–4-0220.