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), there is a question whether administration of liposome-based therapeutic agents interferes with clearance of infectious organisms by the MPS from 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 blood was studied with mice. Classical liposomes (LIP A) and placebo liposomes with lipid composition as in AmBisome (LIP B) or as in Doxil (LIP C) were used. Liposomes were administered intravenously as a single dose. Second, the effect of multiple-dose administration of AmBisome on bacterial blood clearance was studied with rats. AmBisome was administered with two different dosage schedules. The blood clearance capacity of the MPS was monitored at different time points after the last liposome 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 clinically relevant regimen.
van Etten
E W
EW
Department of Medical Microbiology and Infectious Diseases, Erasmus University Rotterdam, The Netherlands. vanetten@kmic.fgg.eur.nl
ten Kate
M T
MT
Snijders
S V
SV
Bakker-Woudenberg
I A
IA
D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D002244:Carbon / Q000378:metabolism; D004337:Drug Carriers / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D007275:Injections, Intravenous; D007711:Klebsiella pneumoniae / Q000276:immunology*; D008081:Liposomes / Q000494:pharmacology*; D008657:Metabolic Clearance Rate / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D010586:Phagocytes / Q000187:drug effects* / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects*; D051381:Rats; D013997:Time Factors
D004337:Drug Carriers; D008081:Liposomes; C068538:liposomal amphotericin B; D002244:Carbon; D000666:Amphotericin B