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

J Liposome Res. 2021 Mar;31(1):1-10. doi: 10.1080/08982104.2019.1682604. Epub 2019 Nov 12.

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; biodistribution; curcumin; doxorubicin; pharmacokinetics.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / adverse effects*
  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / pharmacokinetics*
  • Capsules
  • Carcinoma / drug therapy*
  • Colonic Neoplasms / drug therapy*
  • Curcumin / chemistry*
  • Doxorubicin / adverse effects*
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacokinetics*
  • Liposomes / chemistry
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms, Experimental / drug therapy
  • Particle Size
  • Rats

Substances

  • Antibiotics, Antineoplastic
  • Capsules
  • Liposomes
  • Doxorubicin
  • Curcumin