title: Amphotericin B-entrapping lipid nanoparticles and their in vitro and in vivo characteristics.
abstract: 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 159.1nm according to a variation of their lipid composition. The surface of AmB-entrapping PEG (0.2)-LNPs having 84.4+/-6nm of particle size was negatively charged showing -50.4+/-5mV 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.
authors.affiliation: Center for Drug Discovery Technologies, Korea Research Institute of Chemical Technology, Yuseong, Deajeon, Republic of Korea.
authors.forename: Suk Hyun
authors.initials: SH
authors.lastname: Jung
authors.forename: Deok Hwi
authors.initials: DH
authors.lastname: Lim
authors.forename: Soon Hwa
authors.initials: SH
authors.lastname: Jung
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Kyu-Sung
authors.initials: KS
authors.lastname: Jeong
authors.forename: Hasoo
authors.initials: H
authors.lastname: Seong
authors.forename: Byung Cheol
authors.initials: BC
authors.lastname: Shin
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001228:Aspergillosis / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality; D001232:Aspergillus fumigatus; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D005079:Excipients; D005658:Fungi / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000935:Antifungal Agents; D005079:Excipients; D000666:Amphotericin B