Mixed micellar nanoparticle of amphotericin B and poly styrene-block-poly ethylene oxide reduces nephrotoxicity but retains antifungal activity.
Mixed micellar nanoparticle consisting of amphotericin B (AmB) and poly styrene-block-poly ethylene oxide (PS-block-PEO) was prepared by high pressure homogenizer. Nephrotoxicity of the nanoparticle was investigated along with antifungal activity and self-aggregation status of the drug in the nanoparticle. Nephrotoxicity was markedly reduced when AmB was intravenously administered to rats as mixed micellar nanoparticle with PS-block-PEO in terms of transmission electron microscopy of tubular cells and creatinine clearance. Antifungal activity of AmB was not altered when the drug was in the form of mixed micellar nanoparticle compared to both conventional formulation and AmB micelle treated by same procedure without PS-block-PEO. Self-aggregation status of AmB molecules revealed monomeric in the mixed micellar nanoparticle with PS-block-PEO up to the therapeutic level of the drug (1-3 mM). The reduced nephrotoxicity of AmB in mixed micellar nanoparticle may be associated with the existence of the drug as monomeric form in the nanoparticle. Based on our result, formulation of AmB as mixed micellar nanoparticle with PS-block-PEO may be a promising alternative for the treatment of fungal diseases in patients who are at risk of renal dysfunction.
Han
Kun
K
College of Pharmacy, Chungbuk National University, 12 Gaeshin-dong, Cheonglu, Chungbuk 361-763, Korea.
Miah
M A Jalil
MA
Shanmugam
Srinivasan
S
Yong
Chul Soon
CS
Choi
Han-Gon
HG
Kim
Jung Ae
JA
Yoo
Bong Kyu
BK
D000666:Amphotericin B / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D007275:Injections, Intravenous; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D008823:Micelles; D008826:Microbial Sensitivity Tests; D053758:Nanoparticles; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011137:Polystyrenes / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties
D000935:Antifungal Agents; D004337:Drug Carriers; D008823:Micelles; D011137:Polystyrenes; D011092:Polyethylene Glycols; D000666:Amphotericin B