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.