title: Antitumor activity of doxorubicin encapsulated in poly(ethylene glycol)-coated liposomes.
abstract: The antitumor activity of doxorubicin (DXR) which had been encapsulated in poly(ethylene glycol) (PEP)-coated long-circulating liposomes was examined in mice inoculated with colon 26 carcinoma cells. Six mol% of the distearoylphosphatidylethanolamine derivative of PEGs with different molecular weights was incorporated in liposomes (90-110 nm, mean diameter) composed of distearoylphosphatidylcholine/cholesterol (1/1, molar ratio), and the encapsulating efficiency of DXR in liposomes was more than 98% by the pH gradient method. Each concentration of DXR in blood and tumor tissue was significantly greater after administration of the drug encapsulated in PEG-coated liposomes (DXR-PEG-liposome) compared to the non-coated control liposomes or non-encapsulated free drug. DXR-PEG-liposome prepared with PEG1000 (DXR-PEG1000-liposome) more effectively increased the level of DXR in blood and tumor than did the preparations with PEG5000 or PEG 12000. A single treatment with DXR-PEG1000-liposome (10 mg DXR/kg) resulted in increased survival time. Further therapeutic improvement in terms of tumor growth retardation and prolongation of survival time were observed following multiple treatments with DXR-PEG1000-liposome (3 x 5 mg DXR/kg). Long-circulating liposome coating optimized PEGs should be useful for the delivery of chemotherapeutic agents for the treatment of solid tumors.
authors.affiliation: Department of Pharmacy, Tokyo Medical College Hospital, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Hosoda
authors.forename: S
authors.initials: S
authors.lastname: Unezaki
authors.forename: K
authors.initials: K
authors.lastname: Maruyama
authors.forename: S
authors.initials: S
authors.lastname: Tsuchiya
authors.forename: M
authors.initials: M
authors.lastname: Iwatsuru
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000008:administration & dosage*
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; D011092:Polyethylene Glycols; D004317:Doxorubicin