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Administration of liposomal agents and blood clearance capacity of the mononuclear phagocyte system
E W van Etten1, M T ten Kate, S V Snijders
1Department of Medical Microbiology and Infectious Diseases, Erasmus University Rotterdam, The Netherlands. vanetten@kmic.fgg.eur.nl
Abstract:
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.
Insights
Liposome administration, particularly AmBisome, does not impair the mononuclear phagocyte system's ability to clear bacteria from the blood. Carbon clearance was only affected by high doses of classical liposomes.
Area of Science:
- Pharmacology
- Immunology
- Nanomedicine
Background:
- Liposomes are frequently cleared by the mononuclear phagocyte system (MPS).
- Potential for liposome-based therapeutics to interfere with MPS clearance of pathogens is a concern.
Purpose of the Study:
- To investigate the impact of empty liposome administration on MPS clearance of carbon particles and bacteria.
- To evaluate the effect of single and multiple doses of AmBisome on bacterial clearance in vivo.
Main Methods:
- Mice received single intravenous doses of classical liposomes (LIP A), AmBisome-like (LIP B), or Doxil-like (LIP C) empty liposomes.
- Rats received multiple doses of AmBisome under different schedules.
- Carbon clearance and bacterial clearance from blood were measured at various time points post-administration.
Main Results:
- Single high-dose administration of empty classical liposomes impaired carbon clearance by the MPS.
- Bacterial clearance from blood was not impaired by any of the tested liposome types or administration schedules.
- Prolonged AmBisome treatment, even in clinically relevant regimens, did not affect bacterial blood clearance.
Conclusions:
- Empty liposomes, at high doses, can transiently affect MPS clearance of inert particles.
- Liposome-based therapeutics, including AmBisome, do not compromise the MPS's capacity to clear bacteria from the bloodstream, even with prolonged administration.