title: Tumor-type-dependent vascular permeability constitutes a potential impediment to the therapeutic efficacy of liposomal oxaliplatin.
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.affiliation: Department of Pharmacokinetics and Biopharmaceutics, The University of Tokushima, Tokushima, Japan.
authors.forename: Amr S
authors.initials: AS
authors.lastname: Abu Lila
authors.forename: Haruna
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Doi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Ishida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiwada
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D008081:Liposomes; D008297:Male; D008545:Melanoma / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000077150:Oxaliplatin; D011092:Polyethylene Glycols / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D011092:Polyethylene Glycols