Hosoya K, Kubo H, Natsume H, Sugibayashi K, Morimoto Y
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
Biol Pharm Bull. 1994 Feb;17(2):316-22. doi: 10.1248/bpb.17.316.
The effects of eight prospective absorption enhancers on the nasal mucosa in rabbit have been assessed using an in vitro Ussing chamber technique. Sodium taurodihydrofusidate (STDHF), sodium deoxycholate (DC), polyoxyethylene-9-lauryl ether (BL-9), lysophosphatidylcholine (LPC) and sodium dodecyl sulfate (SDS) were found to possess relatively high protein leaching activity, while sodium glycocholate (GC), sodium taurocholate (TC) and EDTA had relatively low activity. The permeation of fluorescein isothiocyanate-labeled dextran (FD, M.W. 9400) as a model drug across the nasal mucosa was found to be greater in the presence of these enhancers. Their enhancement ratio was found to be in the order of BL-9 > STDHF > SDS > LPC > DC > EDTA > GC > TC, which correlated with the protein leaching activity. The differences in protein leaching and enhancement ratio dependent on the magnitude of change of membrane resistance (delta Rm), indicating that these enhancers damaged the membrane and increased FD permeation. delta Rm thus appears to be a useful indicator by which one can estimate nasal mucosa damage by the enhancers.
采用体外尤斯灌流小室技术评估了八种潜在吸收促进剂对兔鼻黏膜的影响。发现牛磺二氢fusidate钠（STDHF）、脱氧胆酸钠（DC）、聚氧乙烯-9-月桂醚（BL-9）、溶血磷脂酰胆碱（LPC）和十二烷基硫酸钠（SDS）具有相对较高的蛋白质渗漏活性，而甘氨胆酸钠（GC）、牛磺胆酸钠（TC）和乙二胺四乙酸（EDTA）的活性相对较低。在这些促进剂存在的情况下，发现异硫氰酸荧光素标记的葡聚糖（FD，分子量9400）作为模型药物穿过鼻黏膜的渗透率更高。发现它们的增强比率顺序为BL-9 > STDHF > SDS > LPC > DC > EDTA > GC > TC，这与蛋白质渗漏活性相关。蛋白质渗漏和增强比率的差异取决于膜电阻变化量（δRm），表明这些促进剂损害了膜并增加了FD的渗透率。因此，δRm似乎是一种有用的指标，通过它可以评估促进剂对鼻黏膜的损害。
