Investigations on the antitumor efficacy of liposome-associated doxorubicin in murine tumor models.
In this report we review our preclinical studies on the antitumor efficacy of L-DXR, using negatively charged sonicated vesicles. Animal studies indicate that various L-DXR formulations are more active than F-DXR on tumors infiltrating the liver and spleen, organs where liposomes are accumulated, and are equally effective on bone marrow-residing leukemic cells. In contrast, F-DXR was more effective than L-DXR when i.v.-administered, mg-equivalent doses were tested against ascitic and subcutaneously implanted tumors. Intraperitoneal administration of L-DXR was significantly more effective and approximately twofold less toxic than F-DXR in the treatment of an ascitic tumor. The antitumor effect correlated well with differences in drug levels in the relevant anatomic areas. These observations stress the site-specific activity of L-DXR and its dependence on biodistribution factor.
Gabizon
A
A
Sharett Institute of Oncology, Hadassah University Hospital, Jerusalem, Israel.
Goren
D
D
Barenholz
Y
Y
D000818:Animals; D001201:Ascites; D001853:Bone Marrow; D001859:Bone Neoplasms / Q000188:drug therapy; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers; D007942:Leukemia, Experimental / Q000188:drug therapy; D008081:Liposomes; D008113:Liver Neoplasms / Q000188:drug therapy; D008223:Lymphoma / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D013160:Splenic Neoplasms / Q000188:drug therapy
D004337:Drug Carriers; D008081:Liposomes; D004317:Doxorubicin