A simple way to enhance Doxil (R) therapy: Drug release from liposomes at the tumor site by amphiphilic block copolymer

Title
A simple way to enhance Doxil (R) therapy: Drug release from liposomes at the tumor site by amphiphilic block copolymer
Author(s)
김종오Kabanov AV[Kabanov AV]Bronich TK[Bronich TK]Zhao Y[Zhao Y]Alakhova DY[Alakhova DY]
Keywords
PEO TRIBLOCK COPOLYMERS; LIPID-MEMBRANES; PLURONIC P85; ANTISENSE OLIGONUCLEOTIDES; INTERSTITIAL PENETRATION; ENCAPSULATED DOXORUBICIN; STEALTH LIPOSOMES; ANTICANCER AGENTS; XENOGRAFT MODEL; MDR CELLS
Issue Date
201305
Publisher
ELSEVIER SCIENCE BV
Citation
JOURNAL OF CONTROLLED RELEASE, v.168, no.1, pp.61 - 69
Abstract
The antitumor efficacy of Doxil (R) is hindered by the poor release of the active drug from the liposome at the tumor sites. This study investigates a possibility to enhance drug release from the liposomes and increase therapeutic efficacy of Doxil (R) by administering Pluronic block copolymers once the liposomal drug accumulates in the tumor sites. In our study, the fluorescence de-quenching experiments were designed to investigate the drug release from liposome by Pluronic P85. MTT cytotoxicity assay and confocal microscopy images were carried out to determine whether Pluronic P85 could facilitate release of Dox from Doxil r. Anti-tumor growth and distribution of drug were evaluated when Pluronic P85 was injected 1 h, 48 h, or 96 h after the Doxil r administration in A2780 human ovarian cancer xenografts. Addition of Pluronic P85 resulted in release of Dox from the liposomes accompanied with significant increases of Dox delivery and cytotoxic effect in cancer cells. The greatest anti-tumor effect of single injection of Doxil (R) was achieved when Pluronic P85 was administered 48 h after Doxil (R). The confocal tile scanning images of tumor section showed that copolymer treatment induced the release of the drug in the tumors from the vessels regions to the bulk of the tumor. No release of the drug remaining in circulation was observed. Our study has demonstrated a simple approach for localized release of Dox from liposome by Pluronic P85 at the tumor site, which was therapeutically beneficial. (C) 2013 Elsevier B.V. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/25918http://dx.doi.org/10.1016/j.jconrel.2013.02.026
ISSN
0168-3659
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약학대학 > 약학부 > Articles
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