ANTITUMOR-ACTIVITY OF DOXORUBICIN ENCAPSULATED IN POLY(ETHYLENE GLYCOL)-COATED LIPOSOMES

The antitumor activity of doxorubicin (DXR) which had been encapsulate d in poly(ethylene glycol) (PEG)-coated long-circulating liposomes was examined in mice inoculated with colon 26 carcinoma cells. Six mol% o f the distearoylphosphatidylethanolamine derivative of PEGs with diffe rent 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) c ompared to the non-coated control liposomes or non-encapsulated free d rug. DXR-PEG-liposome prepared with PEG1000 (DXR-PEG1000-liposome) mor e effectively increased the level of DXR in blood and tumor than did t he preparations with PEG5000 or PEG12000. A single treatment with DXR- PEG1000-liposome (10 mg DXR/kg) resulted in increased survival time. F urther therapeutic improvement in terms of tumor growth retardation an d prolongation of survival time were observed following multiple treat ments with DXR-PEG1000-liposome (3 x 5 mg DXR/kg). Long-circulating li posome coating optimized PEGs should be useful for the delivery of che motherapeutic agents for the treatment of solid tumors.