Reduced dose-limiting toxicity of intraperitoneal mitoxantrone chemotherapy using cardiolipin-based anionic liposomes

Rae Sung Chang, Jiyeon Kim, Han Young Lee, Su Eun Han, Jinhee Na, Kwangmeyung Kim, Ick Chan Kwon, Young Bong Kim, Yu Kyoung Oh

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Intraperitoneal chemotherapy confers limited clinical benefit as a result of the dose-limiting toxicity of anticancer drugs. We aimed to develop optimized liposomes for mitoxantrone (MTO) administration that provide high encapsulation efficiency and increase the therapeutic index. Cationic MTO was loaded onto anionic liposomes by electrostatic surface complexation. The anticancer activity was evaluated in a peritoneal carcinomatosis model. The retention of MTO at the tumor site was monitored by molecular imaging. MTO loading efficiencies by electrostatic complexation were >95% for all anionic liposomes but <5% for neutral liposomes. Among anionic liposomes, cardiolipin liposomes (CLs) exhibited the strongest binding affinity for MTO, the highest anticancer activity, and the lowest toxicity. MTO delivered by CLs showed prolonged retention at tumor sites. Unlike free MTO showing significant cardiotoxicity, MTO administered in CLs provided negligible cardiotoxicity. CL-mediated delivery may increase the therapeutic index of MTO chemotherapy by prolonged retention and reduced cardiotoxicity. From the Clinical Editor: The authors report the development of optimized liposomes for intraperitoneal mitoxantrone delivery that provides high encapsulation efficiency and increases the therapeutic index. Cardiolipin liposomes exhibited the strongest binding affinity for mitoxantrone, along with the highest anti-cancer activity and lowest toxicity, including negligible cardiotoxicity.

Original languageEnglish
Pages (from-to)769-776
Number of pages8
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume6
Issue number6
DOIs
Publication statusPublished - 2010 Dec

Keywords

  • Cardiolipin liposomes
  • Dose-limiting toxicity
  • Intraperitoneal chemotherapy
  • Mitoxanthrone
  • Prolonged retention

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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