Administration of liposomal agents and the phagocytic function of the mononuclear phagocyte system

Liposomal drugs used in clinical practice are often administered to patients that are immunocompromised and hence, highly susceptible to develop systemic infections. The resident phagocytic cells of the MPS will clear the microorganisms from the blood and thus prevent generalization of the infection as well as mortality. As substantial MPS uptake of liposomes occurs, the question arises whether administration of liposomes, 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 three types of 'empty' liposomes (i.e. devoid of drug), differing in blood residence time, on carbon clearance and bacterial clearance from blood was studied in mice: (1) Classical EPC:PS:Ch (4:1:5) liposomes, 300 nm, (2) placebo liposomes with lipid composition as in AmBisome(R) 100 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 clearance capacity of the MPS was monitored at different time points after the last liposome dose. The data obtained show that carbon blood clearance capacity of the MPS was impaired only at a high lipid dose of empty classical liposomes. Bacterial blood clearance capacity was not impaired, not even after multiple dose treatment with AmBisome(R) or Doxil(R) when administered in a clinically relevant regimen. (C) 1998 Elsevier Science B.V. All rights reserved.