Amphotericin B-entrapping lipid nanoparticles and their in vitro and in vivo characteristics

Lipid nanoparticles (LNPs) as nano-scale drug carriers that can entrap poorly water-soluble drugs such as amphotericin B (AmB) in aqueous solution with high drug entrapment efficiency were developed and their in vitro and in vivo characteristics were investigated. The AmB-entrapping plain, anionic and PEG (polyethylene glycol)-LNPs were prepared by using spontaneous emulsification and solvent evaporation (SESE) method. Mean particle size of the AmB-entrapping LNPs ranged from 72.9 to 159.1 nm according to a variation of their lipid composition. The surface of AmB-entrapping PEG (0.2)-LNPs having 84.4 ± 6 nm of particle size was negatively charged showing −50.4 ± 5 mV of zeta-potential value. Entrapment efficiency of AmB in the PEG-LNPs reached up to 76.5 ± 5%. Cytotoxicity of the AmB-entrapping LNPs against human kidney cells, 293 cells, was lower than those of the commercialized AmB-formulations such as Fungizone® and AmBisome®. Hematotoxicity of the AmB-entrapping LNPs against red blood cells was much lower than that of Fungizone® but comparable to AmBisome®. Antifungal activity in vitro of AmB-entrapping LNPs against Candida albicans and Aspergillus fumigatus was better than the commercialized AmB formulations showing their low minimum inhibitory concentration (MIC) for 90% of growth inhibition of fungi. The AmB-entrapping LNPs increased circulation half life of AmB in blood stream and it was comparable to AmBisome®. Antifungal activity in vivo of the AmB-entrapping PEG-LNPs against Aspergillus fumigatus (ATCC 16424)-infected mice was superior to that of AmBisome®. The drug-entrapping LNPs, especially PEG-LNPs, can be applicable to entrapment of poorly water-soluble drugs and enhancement of therapeutic efficacy by modulating pharmacokinetic behaviors and/or drug-related toxicities.