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Anacardic acid enhances the anticancer activity of liposomal mitoxantrone towards melanoma cell lines – in vitro studies

Authors Legut M, Lipka D, Filipczak N, Piwoni A, Kozubek A, Gubernator J

Received 24 September 2013

Accepted for publication 23 October 2013

Published 23 January 2014 Volume 2014:9(1) Pages 653—668


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Mateusz Legut, Dominik Lipka, Nina Filipczak, Adriana Piwoni, Arkadiusz Kozubek, Jerzy Gubernator

Department of Lipids and Liposomes, Faculty of Biotechnology, University of Wrocław, Wrocław, Poland

Abstract: This paper describes a novel formulation of antineoplastic drug: mitoxantrone loaded into liposomal carriers enriched with encapsulated anacardic acid in the liposomal bilayer using a vitamin C gradient. Anacardic acid is a potent epigenetic agent with anticancer activity. This is the first liposomal formulation to combine an actively encapsulated drug and anacardic acid. The liposomes were characterized in terms of basic parameters, such as size, zeta potential, optimal drug-to-lipid ratio, loading time and temperature, and stability at 4°C and in human plasma in vitro. The formulation was found to be stable, and the loading process was rapid and efficient (drug-to-lipid ratio of up to 0.3 with over 90% efficiency in 5 minutes). The cytotoxicity of these formulations was assessed using the human melanoma cell lines A375 and Hs294T and the normal human dermal fibroblast line. The results showed that anacardic acid and to a smaller extent vitamin C significantly increased the cytotoxicity of the drug towards melanoma compared to ammonium sulfate liposomes. On the other hand, vitamin C and anacardic acid both protected normal cells from damage caused by the drug. The formulation combining anacardic acid, vitamin C, and mitoxantrone showed promising results in terms of cytotoxicity and cytoprotection. Therefore, it has potential for anticancer treatment.

Keywords: anacardic acid, vitamin C, ascorbic acid, liposomes, mitoxantrone, melanoma
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