ADMINISTRATION OF LIPOSOMAL AGENTS AND BLOOD CLEARANCE CAPACITY OF THE MONONUCLEAR PHAGOCYTE SYSTEM

As liposomes are cleared from the circulation to a substantial extent by the phagocytic cells of the mononuclear phagocyte system (MPS), the re is a question whether administration of liposome-based therapeutic agents interferes with clearance of infectious organisms by the MPS fr om blood, In the present study, at first the effect of administration of three types of empty liposomes (devoid of drug), differing in blood residence time, on carbon clearance and bacterial clearance from bloo d was studied with mice, Classical liposomes (LIP A) and placebo lipos omes with lipid composition as in AmBisome (LIP B) or as in Doxil (LIP C) were used. Liposomes were administered intravenously as a single d ose. Second, the effect of multiple-dose administration of AmBisome on bacterial blood clearance was studied with rats. AmBisome was adminis tered with two different dosage schedules. The blood clearance capacit y of the MPS was monitored at different time points after the last lip osome injection. It was shown that the carbon blood clearance capacity of the MPS was impaired only at a high lipid dose of empty classical liposomes. The bacterial blood clearance capacity was never impaired, not even after prolonged treatment with AmBisome administered in a cli nically relevant regimen.