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

• Published in: European journal of pharmaceutical sciences 2009-06, Vol.37 (3), p.313-320
• Main Authors: Jung, Suk Hyun, Lim, Deok Hwi, Jung, Soon Hwa, Lee, Jung Eun, Jeong, Kyu-Sung, Seong, Hasoo, Shin, Byung Cheol
• Format: Article
• Language: English
• Subjects: Amphotericin B; Amphotericin B - administration & dosage; Amphotericin B - pharmacokinetics; Animals; Antifungal activity; Antifungal Agents - administration & dosage; Antifungal Agents - pharmacokinetics; Aspergillosis - drug therapy; Aspergillosis - microbiology; Aspergillosis - mortality; Aspergillus fumigatus; Biological and medical sciences; Cell Line; Cell Survival - drug effects; Chemistry, Pharmaceutical; Cytotoxicity; Excipients; Fungi - drug effects; General pharmacology; Hematotoxicity; Hemolysis - drug effects; Humans; Injections, Intravenous; Lipid nanoparticle; Male; Medical sciences; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Microscopy, Electron, Scanning; Nanoparticles; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Spectrophotometry, Ultraviolet
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2009.02.021

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.