DOXORUBICIN ENTRAPPED IN STERICALLY STABILIZED LIPOSOMES - EFFECTS ONBACTERIAL BLOOD CLEARANCE CAPACITY OF THE MONONUCLEAR PHAGOCYTE SYSTEM

The introduction of long-circulating liposomes sterically stabilized b y 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 l iposomes containing doxorubicin, referred to as DOXIL, Previous studie s performed in rats sheaved that doxorubicin-containing liposomes can exert major toxic effects on the liver macrophage population for a con siderable period of time; a strong impairment of phagocytic function a nd even a substantial depletion of the liver macrophage populations we re observed, In the present study, the phagocytic function of the mono nuclear phagocyte system (MPS) after administration of DOXIL at a clin ically relevant dosage schedule was evaluated in rats, Phagocytic func tion of the MPS was assessed by determining bacterial blood clearance capacity, The observations reported herein show that DOXIL is fairly w ell tolerated regarding bacterial blood clearance capacity of the MPS when administered in a regimen that resembles the clinical setting clo sely, This outcome has important implications with regard to the clini cal utility of the liposomal drug, especially in the restricted contex t of immunocompromised cancer patients who easily develop systemic inf ections and should not be confronted with a therapy-induced reduction of the bacterial blood clearance capacity of the MPS.