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 159.1nm 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.
Jung
Suk Hyun
SH
Center for Drug Discovery Technologies, Korea Research Institute of Chemical Technology, Yuseong, Deajeon, Republic of Korea.
Lim
Deok Hwi
DH
Jung
Soon Hwa
SH
Lee
Jung Eun
JE
Jeong
Kyu-Sung
KS
Seong
Hasoo
H
Shin
Byung Cheol
BC
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
D000935:Antifungal Agents; D005079:Excipients; D000666:Amphotericin B