Lyophilized lecithin based oil-water microemulsions as a new and low toxicdelivery system for amphotericin B

Purpose. To develop and investigate lecithin based oil-water microemulsions as potential amphotericin B (AmB) delivery systems and to evaluate their i n vivo acute toxicity. Methods. AmB was added to the microemulsion and its location was evaluated by partitioning studies and UV-visible spectrophotometric analysis of the d rug. Both, non-lyophilized and reconstituted microemulsions were characteri sed and assessed for their stability. Single-dose acute toxicity of the AmB microemulsion was studied on male albino Webster-derived CD-1. mice and co mpared with Fungizone (R). Results. The studies performed showed that AmB was intercalated on the oil- water interface of the microemulsion as a complex formed with lecithin mole cules. AmB addition did not seem to modify the rheological properties of th e original system, but had an effect on its particle size distribution. Lyo philization of the microemulsion led to an oily cake, easily reconstituted and stable at the conditions studied. Single-dose acute toxicity studies pr oved that the LD50 of AmB microemulsions was of 4 mg kg(-1) of animal weigh t, compared with 1 mg kg(-1) found for Fungizone (R). Conclusions. Lyophilized lecithin based oil-water microemulsions appear to be valuable systems for the delivery of AmB in terms of easy and low-cost m anufacturing, stability and safety compared with the formulations already i n market.