Liposomal mitoxantrone for the local treatment of peritoneal carcinomatosis induced by colon cancer cells in mice.
Since liposomes are slowly resorbed from serous cavities, they may constitute a valuable tool for the treatment of peritoneal carcinomatosis. We prepared mitoxantrone (MXN)-liposomes with various lipid compositions and checked their antitumoral activity on a peritoneal carcinomatosis induced by a colon cancer cell injection (1 x 10(5) C51 cells) in BALB/c mice. MXN entrapment in liposomes was rapid and stable due to its high lipophilicity. MXN carried in phosphatidylcholine: cholesterol (2:1; G-liposomes) displayed a reduced toxicity in mice compared to the free drug. When tested at a non-toxic dose (2 mg/kg), MXN entrapped in G-liposomes proved to be as efficient as the free drug. At a higher MXN dose (3 mg/kg), both G-liposomes and phosphatidylcholine:cholesterol:dipalmitoylphosphatidylethanolamine (7:2:1) liposomes, loaded with MXN, significantly increased the life span of mice compared to the free drug and six other liposome formulations. Increase in the MXN therapeutic index, when used in the liposomal form, could then merit further clinical investigations in regard to patients with malignancies confined to serous cavities.
Genne
P
P
Research Group on Digestive Tumors, INSERM U252, Faculty of Medicine, Dijon, France.
Olsson
N O
NO
Gutierrez
G
G
Duchamp
O
O
Chauffert
B
B
D000818:Animals; D002277:Carcinoma / Q000188:drug therapy; D003110:Colonic Neoplasms; D004337:Drug Carriers; D004563:Electrochemistry; D005260:Female; D008081:Liposomes / Q000737:chemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008942:Mitoxantrone / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D009368:Neoplasm Transplantation; D010534:Peritoneal Neoplasms / Q000188:drug therapy*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D004337:Drug Carriers; D008081:Liposomes; D008942:Mitoxantrone