J. Hosoda et al., ANTITUMOR-ACTIVITY OF DOXORUBICIN ENCAPSULATED IN POLY(ETHYLENE GLYCOL)-COATED LIPOSOMES, Biological & pharmaceutical bulletin, 18(9), 1995, pp. 1234-1237
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.