ADMINISTRATION OF LIPOSOMAL AGENTS AND THE PHAGOCYTIC FUNCTION OF THEMONONUCLEAR PHAGOCYTE SYSTEM

Liposomal drugs used in clinical practice are often administered to pa tients that are immunocompromised and hence, highly susceptible to dev elop systemic infections. The resident phagocytic cells of the MPS wil l clear the microorganisms from the blood and thus prevent generalizat ion of the infection as well as mortality. As substantial MPS uptake o f liposomes occurs, the question arises whether administration of lipo somes, particularly those containing potentially toxic agents such as amphotericin B and doxorubicin, affect the phagocytic capacity of the MPS. In the present study, at first the effect of administration of th ree types of 'empty' liposomes (i.e. devoid of drug), differing in blo od residence time, on carbon clearance and bacterial clearance from bl ood was studied in mice: (1) Classical EPC:PS:Ch (4:1:5) liposomes, 30 0 nm, (2) placebo liposomes with lipid composition as in AmBisome(R) 1 00 nm, and (3) placebo liposomes with lipid composition as in Doxil(R) , 100 nm. Liposomes were administered i.v. as a single dose. Secondly, the effect of multiple dose administration of AmBisome(R) or Doxil(R) on bacterial clearance from blood was studied in rats. AmBisome(R) or Doxil(R) were administered at various dosage schedules. Blood clearan ce capacity of the MPS was monitored at different time points after th e last liposome dose. The data obtained show that carbon blood clearan ce capacity of the MPS was impaired only at a high lipid dose of empty classical liposomes. Bacterial blood clearance capacity was not impai red, not even after multiple dose treatment with AmBisome(R) or Doxil( R) when administered in a clinically relevant regimen. (C) 1998 Elsevi er Science B.V. All rights reserved.