Evaluation of bile acids and fusidate derivative as nasal absorption enhancers using an electrophysiological technique

The present study was carried out to investigate the reversibility of the a ction of two nasal absorption enhancers, bile acids and fusidate derivative , on nasal membrane resistance, The nasal mucosa was isolated from rabbit n asal septum and mounted in a Ussing-type chamber to allow the monitoring of the membrane resistance and flux of fluorescein isothiocyanate-labeled dex tran (FD10, M.W. 9400), Membrane resistance was reduced by 46% following tr eatment with 0.5% (w/v) sodium taurodihydrofusidate (STDHF) for 10 min and then gradually returned to the control level after being wash, The resistan ce was restored to 76% of the control level following a 30 min treatment wi th 0.5% (w/v) STDHF, However, there was no recovery of resistance following treatment with 0.5% (w/v) STDHF for 120 min or 1% (w/v) STDHF for 10 min. Concurrently, FD10 transport was enhanced while membrane resistance was red uced. Treatment with 0.5% (w/v) sodium deoxycholate (DC) for more than 10 m in showed no reversible action and marked FD10 transport enhancement, where as a 10-30 min treatment with 0.5% (w/v) sodium glycocholate (GC) or sodium taurocholate (TC) resulted in the rapid recovery of membrane resistance wi thout any enhancement of FD10 permeation. STDHF transport across the nasal mucosa was similar to 2-fold faster than that of DC, GC, and TC, The accumu lation of STDHF in the nasal mucosa was 2-fold lower than that of DC and 1. 7-fold higher than that of GC acid TC after a 30 min treatment, The rank or der of hydrophobicity determined by reverse-phase HPLC was: DC>STDHF>GC>TC, These results suggest that the reduction in membrane resistance and its re versibility appear to be due to a balance between the accumulation and clea rance of STDHF.