title: Effective anti-tumor activity of oxaliplatin encapsulated in transferrin-PEG-liposome.
abstract: Oxaliplatin (trans-L-diaminocyclohexane oxalatoplatinum, L-OHP) is a novel cisplatin derivative that can improve the side effects of cisplatin such as toxicity to the kidneys and peripheral nerve system. However, L-OHP is effective only when combined with 5-Fluorouracil (5-FU) and Leucovorin. The relatively low anti-tumor index of L-OHP alone is because low levels accumulate in tumor tissues due to high partitioning to erythrocytes in vivo. A successful outcome of cancer therapy using L-OHP requires the selective delivery of a relatively high concentration of the drug to tumors. The present study examines tumor-selective delivery of L-OHP using liposomes modified with transferrin-conjugated polyethyleneglycol (TF-PEG-liposomes). Delivery using these liposomes significantly reduced L-OHP partitioning to erythrocytes and improved the circulation time of L-OHP in vivo, resulting in enhanced extravasation of liposomes into tumors. The TF-PEG-liposomes maintained a high L-OHP concentration in tumors for over 72 h after intravenous injection, which was longer than that of the liposomes modified with PEG (PEG-liposomes). Intravenously administered L-OHP encapsulated within TF-PEG-liposomes (L-OHP: 5 mg/kg) suppressed tumor growth more effectively than PEG-liposomes, Bare-liposomes and free L-OHP. Although L-OHP is usually combined with 5-FU and Leucovorin, our results suggest that L-OHP encapsulated within TF-PEG-liposomes has potential for cancer therapy.
authors.affiliation: Department of Biopharmaceutics, School of Pharmaceutical Sciences, Teikyo University, 1091-1 Suwarashi, Sagamiko, Sagamihara, Kanagawa 229-0195, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Suzuki
authors.forename: Tomoko
authors.initials: T
authors.lastname: Takizawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kuwata
authors.forename: Mahito
authors.initials: M
authors.lastname: Mutoh
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ishiguro
authors.forename: Naoki
authors.initials: N
authors.lastname: Utoguchi
authors.forename: Atsuko
authors.initials: A
authors.lastname: Shinohara
authors.forename: Masazumi
authors.initials: M
authors.lastname: Eriguchi
authors.forename: Hironobu
authors.initials: H
authors.lastname: Yanagie
authors.forename: Kazuo
authors.initials: K
authors.lastname: Maruyama
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004912:Erythrocytes / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008081:Liposomes; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077150:Oxaliplatin; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution; D014168:Transferrin / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D009944:Organoplatinum Compounds; D014168:Transferrin; D000077150:Oxaliplatin; D011092:Polyethylene Glycols