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Tumor-type-dependent vascular permeability constitutes a potential impediment to the therapeutic efficacy of liposomal oxaliplatin
Faculty
Not Specified
Year:
2012
Type of Publication:
Article
Pages:
524-531
Authors:
Ishida, Tatsuhiro, Kiwada, Hiroshi, Abu Lila, Amr S, Matsumoto, Haruna, Doi, Yusuke, Nakamura, Hiroyuki
DOI:
10.1016/j.ejpb.2012.04.010
Journal:
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS ELSEVIER SCIENCE BV
Volume:
81
Research Area:
Pharmacology \& Pharmacy
ISSN
ISI:000307040900008
Keywords :
Antitumor activity, Oxaliplatin, PEG-coated liposomes, Tumor localization, Vascular permeability
Abstract:
The delivery of anticancer agents to solid tumors is problematic. Nanomolecular drug carriers represent an attractive alternative strategy for efficient anticancer drug delivery to tumor tissue, because they appear to target tumors and have limited toxicity in normal tissue. However, inadequate and heterogeneous distribution of nanocarriers in tumor tissue is a major impediment for their efficient use in clinical cancer therapy. In the present study, we examined the effect of tumor type on the intratumor accumulation and distribution of polyethylene glycol (PEG)-coated liposomes using in vivo mouse models of three cancer cell lines: colon adenocarcinoma (C26), Lewis lung carcinoma (LLC), and B16BL6 melanoma (B16BL6). The tumor growth inhibition and the apoptotic response of oxaliplatin (I-OHP) encapsulated in the PEG-coated liposomes were tumor type dependent and correlated with a tendency toward tumor accumulation and intratumor distribution of PEG-coated liposome, in contrast to in vitro cytotoxicity of I-OHP. A potent antitumor effect observed in both C26 and LLC tumor-bearing mice was attributed to the enhanced extravasation with subsequent preferential accumulation of PEG-coated liposomes through tumor vasculature with high permeability. Our results suggest that the permeability of tumor vasculature constitutes a potential impediment to tumor localization and thereby to the antitumor efficacy of PEG-coated liposomal anticancer drugs. (C) 2012 Elsevier B.V. All rights reserved.
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