Antitumor Activity of Doxorubicin Encapsulated in Poly (ethylene glycol)-Coated Liposomes

• Published in: Biological & pharmaceutical bulletin Vol. 18; no. 9; pp. 1234 - 1237
• Main Authors: MARUYAMA, Kazuo, UNEZAKI, Sakae, IWATSURU, Motoharu, HOSODA, Junichi, TSUCHIYA, Seishi
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 1995; Maruzen; Japan Science and Technology Agency
• Subjects: Animals; Antibiotics, Antineoplastic - administration & dosage; Antineoplastic agents; Biological and medical sciences; Chemotherapy; doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - pharmacokinetics; Drug Carriers; drug delivery system; liposome; Liposomes; long-circulating liposome; Male; Medical sciences; Mice; Mice, Inbred BALB C; Neoplasms, Experimental - drug therapy; Pharmacology. Drug treatments; poly (ethylene glycol); Polyethylene Glycols - administration & dosage; Antineoplastic agent; Control release polymer; Rodentia; Liposome; Drug carrier; Biological activity; Ethylene oxide polymer; Vertebrata; Mammalia; Mouse; Animal; Formulation; Dosage form; Anthracyclins; Pharmacokinetics
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.18.1234

The antitumor activity of doxorubicin (DXR) which had been encapsulated in poly (ethylene glycol) (PEG)-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 (90-110nm, 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 PEG12000. A single treatment with DXR-PEG1000-liposome (10mg 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 (3×5mg DXR/kg). Long-circulating liposome coating optimized PEGs should be useful for the delivery of chemotherapeutic agents for the treatment of solid tumors.