BACKGROUND: Stealth liposomes hold promise as a mode of delivering cytotoxic agents selectively to tumors in cancer patients. The objective of this study was to determine whether stealth liposomal doxorubicin accumulates selectively in bone metastases based on clinical material obtained from two patients with breast carcinoma. METHODS: Tumor tissue was obtained from two women (ages 33 years and 41 years, respectively) with metastatic breast carcinoma who responded to treatment with stealth liposomal doxorubicin and later underwent a surgical fixation procedure to treat a pathologic fracture of the femur. Drug levels in the tumor and adjacent muscle were examined by high performance liquid chromatography analysis in both patients and by fluorescence microscopy in one of the patients. RESULTS: Bone tumor fragments obtained during surgery performed 6 days after the administration of the 12th course of stealth liposomal doxorubicin in 1 patient and 12 days after the administration of the 16th course of stealth liposomal doxorubicin in the second patient had a 10-fold greater concentration of liposomal doxorubicin than tumor free muscle. Doxorubicin fluorescence and specific nuclear staining showed good colocalization, thus confirming the presence of the liposome-delivered drug in the nuclei of tumor cells. CONCLUSIONS: Using skeletal muscle as a comparator, stealth liposomal doxorubicin accumulates selectively in metastatic breast carcinoma cells within bone.
BACKGROUND: Stealth liposomes hold promise as a mode of delivering cytotoxic agents selectively to tumors in cancerpatients. The objective of this study was to determine whether stealth liposomal doxorubicin accumulates selectively in bone metastases based on clinical material obtained from two patients with breast carcinoma. METHODS:Tumor tissue was obtained from two women (ages 33 years and 41 years, respectively) with metastatic breast carcinoma who responded to treatment with stealth liposomal doxorubicin and later underwent a surgical fixation procedure to treat a pathologic fracture of the femur. Drug levels in the tumor and adjacent muscle were examined by high performance liquid chromatography analysis in both patients and by fluorescence microscopy in one of the patients. RESULTS: Bone tumor fragments obtained during surgery performed 6 days after the administration of the 12th course of stealth liposomal doxorubicin in 1 patient and 12 days after the administration of the 16th course of stealth liposomal doxorubicin in the second patient had a 10-fold greater concentration of liposomal doxorubicin than tumor free muscle. Doxorubicin fluorescence and specific nuclear staining showed good colocalization, thus confirming the presence of the liposome-delivered drug in the nuclei of tumor cells. CONCLUSIONS: Using skeletal muscle as a comparator, stealth liposomal doxorubicin accumulates selectively in metastatic breast carcinoma cells within bone.
Authors: Frederik Soetaert; Preethi Korangath; David Serantes; Steven Fiering; Robert Ivkov Journal: Adv Drug Deliv Rev Date: 2020-06-27 Impact factor: 15.470
Authors: Donald A Richards; David Loesch; Svetislava J Vukelja; Hillary Wu; William J Hyman; Jeffery Nieves; Yunfei Wang; Simin Hu; Oluwatoyin O Shonukan; Datchen F Tai Journal: Invest New Drugs Date: 2010-03-30 Impact factor: 3.850
Authors: Eman Alaaeldin; Amr S Abu Lila; Naoto Moriyoshi; Hatem A Sarhan; Tatsuhiro Ishida; Khaled A Khaled; Hiroshi Kiwada Journal: Pharm Res Date: 2013-05-15 Impact factor: 4.200
Authors: Robert T O'Donnell; Shiloh M Martin; Yunpeng Ma; William C Zamboni; Joseph M Tuscano Journal: Invest New Drugs Date: 2009-03-24 Impact factor: 3.850