Mixed Micellar Nanoparticle of Amphotericin B and Poly Styrene-block-poly Ethylene Oxide Reduces Nephrotoxicity but Retains Antifungal Activity

다국어 초록 (Multilingual Abstract)

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.

참고문헌 (Reference)

• 1 "What is the current and future status of conventional amphotericin B?" 27 : 12-16, 2006
• 2 "Treatment of murine candidiasis and cryptococcosis with amphotericin B incorporated into egg lecithin-bile salt mixed micelles. Antimicrob. Agents Chemother." 294-299, 1994
• 3 "The impact of nanobiotechnology on the development of new drug delivery systems" 6 : 3-5, 2005
• 4 "The effect of surfactants on the aggregation state of amphotericin B. Biochim. Biophys. Acta." 289-295, 1990
• 5 "The efect of surfactants on the aggregation state of amphotericin B" 29 : 681-685, 2001
• 6 "Structure of amphotericin B aggregates as revealed by UV and CD spectroscopies. Biopolymers" 1575-1588, 1981
• 7 "Structural studies on aqueous and hydro alcoholic solutions of a polyene antibiotic" 2419-2427, 1977
• 8 "Pharmaceutical nanotechnology: polymeric vesicles for drug and gene delivery" 3 : 629-640, 2006
• 9 "Organization of Dispersions of a Linear Diblock Copolymer of Polystyrene and Poly(ethylene oxide) at the Air-Water Micellar Nanoparticle of Amphotericin B and PS-block-PEO 1349" 31 : 7851-7864, 1998
• 10 "One-sided action of amphotericin B on cholesterol-containing mem- branes is determined by its self-association in the medium. Biochemistry" 5707-5715, 1991
• 11 "Micelle/monomer control over the membrane-" ja (ja):
• 12 "Management of systemic fungal infections: alternatives to itraconazole" 56 : i39-i48, 2005
• 13 "Effects of the aggrega- tion state of amphotericin B on its toxicity to mice. Antimicrob. Agents Chemother." 2310-2315, 1992
• 14 "Comparison of the efficacies of various formulations of amphotericin B against murine visceral leishmaniasis.Antimicrob" 41 : 2089-2092, 1997
• 15 "Comparative efficacies, toxicities, and tissue concentrations of amphotericin B lipid formulations in a murine pulmonary aspergillosis model" 50 : 2122-2131, 2006
• 16 "Clinical significance of nephrotoxicity in patients treated with amphotericin B for suspected or proven aspergillosis" 29 : 1402-1407, 1999
• 17 "Candidemia at a tertiary-care hospital: epidemiology, treatment, clinical outcome and risk factors for death" 21 : 767-774, 2002
• 18 "Biodistribution of amphotericin B when delivered through cholesterol hemisucinate vesicles in normal and A. fumigatus infected mice" 17 : 1236-1242, 2000