Doxorubicin entrapped in sterically stabilized liposomes: effects on bacterial blood clearance capacity of the mononuclear phagocyte system.
The introduction of long-circulating liposomes sterically stabilized by surface coating with polyethylene glycol has expanded the potential for drug targeting to tumors. In recent clinical studies, evidence of significant antitumor activity has been obtained with the industrially prepared formulation of long-circulating polyethylene glycol-coated liposomes containing doxorubicin, referred to as DOXIL. Previous studies performed in rats showed that doxorubicin-containing liposomes can exert major toxic effects on the liver macrophage population for a considerable period of time; a strong impairment of phagocytic function and even a substantial depletion of the liver macrophage populations were observed. In the present study, the phagocytic function of the mononuclear phagocyte system (MPS) after administration of DOXIL at a clinically relevant dosage schedule was evaluated in rats. Phagocytic function of the MPS was assessed by determining bacterial blood clearance capacity. The observations reported herein show that DOXIL is fairly well tolerated regarding bacterial blood clearance capacity of the MPS when administered in a regimen that resembles the clinical setting closely. This outcome has important implications with regard to the clinical utility of the liposomal drug, especially in the restricted context of immunocompromised cancer patients who easily develop systemic infections and should not be confronted with a therapy-induced reduction of the bacterial blood clearance capacity of the MPS.
Storm
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Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands.
ten Kate
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Working
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Bakker-Woudenberg
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D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D016470:Bacteremia / Q000276:immunology*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000633:toxicity; D004337:Drug Carriers; D005260:Female; D008081:Liposomes; D010586:Phagocytes / Q000187:drug effects* / Q000276:immunology; D051381:Rats
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; D004317:Doxorubicin