Chemotherapy with hybrid liposomes without any drug in vivo

Abstract

Prolonged survival was seen in a carcinoma model in mice intraperitoneally inoculated with B-16 melanoma cells after the intraperitoneal treatment with hybrid liposomes composed of L-alpha-dimyristoylphosphatidylcholine (DMPC) and polyoxyethylenedodecyl ether (C12(EO)n, n = 10 and 23 respectivery) which had a uniform and stable structure. No drug was administered. The therapeutic effects of the single-component liposomes composed of lipids with a variety of hydrophilic head groups and different hydrophobic alkyl chains were investigated. Markedly prolonged survival (248%) of mice was achieved after treatment with DMPC liposomes. However, DMPC liposomes have the disadvantage of an unstable structure, requiring daily sonication. On the other hand, no life-prolonging effects or toxicity occurred with the administration of the other single-component liposome employed in this study. Next, we successfully prepared stable, uniform liposomes composed of 90 mol% DMPC and 10 mol% C12(EO)n (n = 10 and 23, respectively), which have diameters of 70 nm and 100 nm, respectively. Interestingly, prolonged survival (173-186%) of mice was achieved after treatment with hybrid liposomes of 90 mol% DMPC/10 mol% C12(EO)n (n = 10 and 23). Finally, we conducted toxicity tests using normal rats to determine hybrid liposome stability. There were no abnormal findings in blood chemistry or relative organ weights at autopsy of normal rats after hybrid liposome administration. In addition, hybrid liposomes were metabolized in the liver after intravenous administration to normal mice. These results suggest that hybrid liposomes could be used as a new single chemotherapeutic agent in the treatment of carcinoma with no side effects.