Intraperitoneal administration of doxorubicin encapsulating liposomes against peritoneal dissemination.
To improve therapy for peritoneal dissemination, and the distributions of doxorubicin (DOX) in the abdominal cavity, solid tumor and normal tissues after intraperitoneal administration of DOX-encapsulating liposomes was examined. In small negatively charged liposomes, lipid composition did not affect the clearance or stability of liposomes in the abdominal cavity. Whereas, for the treatment of solid tumor and the reduction of side effects, L-alpha-distearoylphosphatidylcholine-containing liposomes were most effective. On the other hand, large liposomes (DS(L)-Lip) were most abundant in the abdominal 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 abdominal cavity and DOX was released from the liposomes. DS(L)-Lip remain in the abdominal cavity for a long time inducing cytotoxicity. The survival of Ehrlich 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 dissemination in the abdominal cavity, respectively.
Sadzuka
Y
Y
School of Pharmaceutical Sciences, University of Shizuoka, Japan. sadzuka@ys7.u-shizuoka-ken.ac.jp
Hirota
S
S
Sonobe
T
T
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers; D007274:Injections, Intraperitoneal; D008081:Liposomes; D008297:Male; D051379:Mice; D010316:Particle Size; D010534:Peritoneal Neoplasms / Q000517:prevention & control*
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; D004317:Doxorubicin