title: Effects of fluidity and vesicle size on antitumor activity and myelosuppressive activity of liposomes loaded with daunorubicin.
abstract: The effects of fluidity and vesicle size on the antitumor activity and myelosuppressive activity of liposomes loaded with daunorubicin, an anthracycline antitumor drug, were investigated in Yoshida sarcoma-bearing rats. Liposomes composed of egg phosphatidylcholine (EPC) or hydrogenated egg phosphatidylcholine (HEPC), cholesterol and dicetyl phosphate in a molar ratio of 5:4:1 were injected intravenously into rats 5 d after subcutaneous inoculation of Yoshida sarcoma. At non-effect dosage in free drug, HEPC-liposomes with a diameter of 58 or 142 nm showed the greatest inhibitory effect against Yoshida sarcoma among liposomes tested, whereas larger ones (272 nm) had weaker effect. Small EPC-liposomes (57 nm) had no effect. Larger HEPC-liposomes (especially 142 nm) greatly decreased the number of peripheral white blood cell compared with free drug at the same dose, indicating relatively strong myelosuppressive toxicity. However, small EPC- and HEPC-liposomes with a diameter of 57 and 58 nm, respectively, showed toxic effects comparable to that of free drug. Examination of the dose-dependency of therapeutic effects and toxicity indicated encapsulation of daunorubicin in the small HEPC-liposomes to enhance the therapeutic index about 3 times that of free drug. These findings indicate the possibility of using small HEPC-liposome as a drug carrier for targeting solid tumors.
authors.affiliation: Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Nagayasu
authors.forename: T
authors.initials: T
authors.lastname: Shimooka
authors.forename: Y
authors.initials: Y
authors.lastname: Kinouchi
authors.forename: K
authors.initials: K
authors.lastname: Uchiyama
authors.forename: Y
authors.initials: Y
authors.lastname: Takeichi
authors.forename: H
authors.initials: H
authors.lastname: Kiwada
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D003630:Daunorubicin / Q000008:administration & dosage* / Q000494:pharmacology / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D008081:Liposomes; D008297:Male; D008560:Membrane Fluidity; D051381:Rats; D012517:Sarcoma, Yoshida / Q000188:drug therapy
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D003630:Daunorubicin