Intraperitoneal administration of doxorubicin encapsulating liposomes against peritoneal dissemination

To improve therapy for peritoneal dissemination, and the distributions of d oxorubicin (DOX) in the abdominal cavity, solid tumor and normal tissues af ter intraperitoneal administration of DOX-encapsulating liposomes was exami ned. In small negatively charged liposomes, lipid composition did not affec t the clearance or stability of liposomes in the abdominal cavity. Whereas, for the treatment of solid tumor and the reduction of side effects, L-alph a-disteafoylphosphatidylcholine-containing liposomes were most effective. O n the other hand, large liposomes (DS(L)-Lip) were most abundant in the abd ominal cavity. As the DOX levels in the heart, liver and solid tumor after DS(L)-Lip injection were lower than the corresponding values for the small liposome group, we considered that DS(L)-Lip were disrupted in the abdomina l cavity and DOX was released from the liposomes. DS(L)-Lip remain in the a bdominal cavity for a long time inducing cytotoxicity. The survival of Ehrl ich ascites carcinoma-bearing mice was considered to be prolonged by DS(L)- Lip. Liposomes, both small and large in size appear to be effective against solid tumors except in the abdominal cavity, and against peritoneal dissem ination in the abdominal cavity, respectively. (C) 2000 Elsevier Science Ir eland Ltd. All rights reserved.