Protective and antifungal properties of Nanodisk-Amphotericin B over commercially available Amphotericin B

作     者：Do-Yeon Cho Kyle J.Hoffman Gobind S.Gill Dong-Jin Lim Daniel Skinner Calvin Mackey Steven M.Rowe Bradford A.Woodworth 

作者机构：Department of Otolaryngology Head & Neck SurgeryUniversity of Alabama at BirminghamBirminghamALUSAGregory Fleming James Cystic Fibrosis Research CenterUniversity of Alabama at BirminghamBirminghamALUSA Department of Otolaryngology Head & Neck SurgeryUniversity of Alabama at BirminghamBirminghamALUSA Gregory Fleming James Cystic Fibrosis Research CenterUniversity of Alabama at BirminghamBirminghamALUSADepartments of MedicinePediatricsCell Developmental and Integrative BiologyUniversity of Alabama at BirminghamBirminghamALUSA 

出 版 物：《World Journal of Otorhinolaryngology-Head and Neck Surgery》 (世界耳鼻咽喉头颈外科杂志（英文）)

年 卷 期：2017年第3卷第1期

页      面：-页

学科分类：1003[医学-口腔医学] 1002[医学-临床医学] 

基　　金：CF Research Center John W. Kirklin Research and Education Foundation National Institutes of Health, NIH National Heart, Lung, and Blood Institute, NHLBI, (1 R01 HL133006-01) National Heart, Lung, and Blood Institute, NHLBI National Institute of Diabetes and Digestive and Kidney Diseases, NIDDK, (5P30DK072482-04) National Institute of Diabetes and Digestive and Kidney Diseases, NIDDK University of Alabama at Birmingham, UAB 

主　　题：Chronic rhinosinusitis Amphotericin Drug delivery Transepithelial ion transport Sinusitis Sinus epithelium Mucociliary clearance Ciliary beat frequency 

摘      要：Objective:Amphotericin B (AMB),a potent antifungal agent,has been employed as topical and systemic therapy for sinonasal fungal infections.A novel formulation of nanodisc (ND) containing super aggregated AMB (ND-AMB) for the treatment of fungal infections has been recently developed to provide greater protection from AMB toxicity than current,clinically approved lipid-based *** objective of the current study was to evaluate the safety and potency of ND-AMB for sinonasal delivery using an in vitro ***:Human sinonasal tissue was harvested during endoscopic sinus surgery and grown at air-liquid interface until *** were exposed to ND-AMB vs AMB and changes in K+ permeability and resistance were measured and recorded via Ussing chamber *** beat frequency (CBF) was analyzed in parallel as well as cytotoxic *** was assessed using real-time PCR measurement of the Aspergillus fumigatus 18S ***:Ussing chamber studies revealed K+ currents that increased rapidly within 30 s of adding AMB (10 μg/mL) to the apical side,indicating apical membranes had become permeable to K+ *** contrast,negligible induction of K+ current was obtained following addition of NDAMB [AMB =(107.7 ± 15.9) μA/cm2 AMB vs ND-AMB =(2.3 ± 0.7) μA/cm2 ND-AMB;P =0.005].ND-AMB also protected nasal epithelial cells from cytotoxicity of AMB (P 0.05).There was no difference in ciliary beat frequency between the two groups (P =0.96).The expression of *** 18S rRNA with exposure of lower dose of ND-AMB was significantly lower compared to that with AMB (P 0.05).Conclusions:Data from the present study suggests ND-AMB protects human nasal epithelia membranes from AMB toxicity by protecting against apical cell K+ permeability while maintaining uncompromised antifungal property compared to ***-AMB could provide a novel topical therapy for sinonasal fungal diseases.