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Tumor-type-dependent vascular permeability constitutes a potential impediment to the therapeutic efficacy of liposomal oxaliplatin.
Eur J Pharm Biopharm. 2012 Aug; 81(3):524-31.EJ

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 (l-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 l-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.

Authors+Show Affiliations

Department of Pharmacokinetics and Biopharmaceutics, The University of Tokushima, Tokushima, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22554766

Citation

Abu Lila, Amr S., et al. "Tumor-type-dependent Vascular Permeability Constitutes a Potential Impediment to the Therapeutic Efficacy of Liposomal Oxaliplatin." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 81, no. 3, 2012, pp. 524-31.
Abu Lila AS, Matsumoto H, Doi Y, et al. Tumor-type-dependent vascular permeability constitutes a potential impediment to the therapeutic efficacy of liposomal oxaliplatin. Eur J Pharm Biopharm. 2012;81(3):524-31.
Abu Lila, A. S., Matsumoto, H., Doi, Y., Nakamura, H., Ishida, T., & Kiwada, H. (2012). Tumor-type-dependent vascular permeability constitutes a potential impediment to the therapeutic efficacy of liposomal oxaliplatin. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 81(3), 524-31. https://doi.org/10.1016/j.ejpb.2012.04.010
Abu Lila AS, et al. Tumor-type-dependent Vascular Permeability Constitutes a Potential Impediment to the Therapeutic Efficacy of Liposomal Oxaliplatin. Eur J Pharm Biopharm. 2012;81(3):524-31. PubMed PMID: 22554766.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tumor-type-dependent vascular permeability constitutes a potential impediment to the therapeutic efficacy of liposomal oxaliplatin. AU - Abu Lila,Amr S, AU - Matsumoto,Haruna, AU - Doi,Yusuke, AU - Nakamura,Hiroyuki, AU - Ishida,Tatsuhiro, AU - Kiwada,Hiroshi, Y1 - 2012/04/25/ PY - 2012/02/17/received PY - 2012/04/15/revised PY - 2012/04/17/accepted PY - 2012/5/5/entrez PY - 2012/5/5/pubmed PY - 2012/12/22/medline SP - 524 EP - 31 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 81 IS - 3 N2 - 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 (l-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 l-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. SN - 1873-3441 UR - https://www.unboundmedicine.com/medline/citation/22554766/Tumor_type_dependent_vascular_permeability_constitutes_a_potential_impediment_to_the_therapeutic_efficacy_of_liposomal_oxaliplatin_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-6411(12)00124-5 DB - PRIME DP - Unbound Medicine ER -