EFFECTS OF FLUIDITY AND VESICLE SIZE ON ANTITUMOR-ACTIVITY AND MYELOSUPPRESSIVE ACTIVITY OF LIPOSOMES LOADED WITH DAUNORUBICIN

The effects of fluidity and vesicle size on the antitumor activity and myelosuppressive activity of liposomes loaded with daunorubicin, an a nthracycline antitumor drug, were investigated in Yoshida sarcoma-bear ing rats. Liposomes composed of egg phosphatidylcholine (EPC) or hydro genated egg phosphatidylcholine (HEPC), cholesterol and dicetyl phosph ate in a molar ratio of 5: 4: 1 were injected intravenously into rats 5 d after subcutaneous inoculation of Yoshida sarcoma. At non-effect d osage in free drug, HEPC-liposomes with a diameter of 58 or 142 nm sho wed the greatest inhibitory effect against Yoshida sarcoma among lipos omes tested, whereas larger ones (272 nm) had weaker effect. Small EPC -liposomes (57 nm) had no effect. Larger HEPC-liposomes (especially 14 2 nm) greatly decreased the number of peripheral white blood cell comp ared with free drug at the same dose, indicating relatively strong mye losuppressive toxicity. However, small EPC- and HEPC-liposomes with a diameter of 57 and 58 nm, respectively, showed toxic effects comparabl e to that of free drug. Examination of the dose-dependency of therapeu tic effects and toxicity indicated encapsulation of daunorubicin in th e small HEPC-liposomes to enhance the therapeutic index about 3 times that of free drug. These findings indicate the possibility of using sm all HEPC-liposome as a drug carrier for targeting solid tumors.