Amphotericin B encapsulated in polyethylene glycol-immunoliposomes for infectious diseases

Abstract Liposomal amphotericin B (L-AmB) is useful for clinical applications because of the decreased toxicity of amphotericin B (AmB). However, liposomes are rapidly removed from the circulation by the reticulo-endothelial system (RES), and show poor targetability to other organs. Recently, some modifications were made to liposomes to correct this disadvantage. Liposomes with polyethylene glycol (PEG-L) have reduced RES uptake and show prolonged circulation time. Liposomes with monoclonal antibody (MoAb) are expected to have active targetability, but are easily captured by the RES. We evaluated the pharmacokinetics and efficacy of the novel targetable liposome 34A-PEG-L modified with polyethylene glycol conjugated with MoAb, 34A, which is specific to murine pulmonary endothelia, in murine pulmonary aspergillosis. The concentrations of AmB in lung were higher in 34A-PEG-L-AmB than those of PEG-L-AmB and L-AmB. 34A-PEG-L-AmB showed the highest efficacy compared to PEG-L-AmB and L-AmB. These results suggest a high targetability for 34A-PEG-L-AmB to lungs of mice.