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

Title
Reduced dose-limiting toxicity of intraperitoneal mitoxantrone chemotherapy using cardiolipin-based anionic liposomes
Authors
장래성김지연이한영한수은나진희김광명권익찬김영봉오유경
Keywords
Intraperitoneal chemotherapy; Mitoxanthrone; Cardiolipin liposomes; Dose-limiting toxicity; Prolonged retention
Issue Date
2010-12
Publisher
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Citation
VOL 6, 769-777
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.
URI
http://pubs.kist.re.kr/handle/201004/40280
ISSN
1549-9634
Appears in Collections:
KIST Publication > Article
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