The enhancing effect of soybean-derived sterylglucoside and beta-sitosterol beta-D-glucoside on nasal absorption in rabbits

The aim of this study was to elucidate the efficiency of soybean-derived st erylglucoside (SG) and its main component beta-sitosterol beta-D-glucoside (Sit-G), as nasal absorption enhancers. Nasal administration of verapamil w ith SG and Sit-G showed the higher bioavailabilities (60.4 and 90.7%, respe ctively) than that with lactose (39.8%). It was clear that SG and Sit-C pro moted the absorption of verapamil through nasal mucosa. To elucidate the me chanism, we measured the calcein leakage from liposomes by incubation with SG, Sit-G, oleic acid, soybean-derived sterol, and beta-sitosterol to inves tigate transcellular absorption and measured the changes in intracellular C a2+ concentrations ([Ca2+]i) by Sit-G to analyze paracellular absorption. T he large amount of calcein leakage induced by enhancers was consistent with an enhancement of bioavailability of verapamil and insulin following nasal administration (oleic acid < SG < Sit-G). Moreover, Sit-G increased [Ca2+] i in the medium containing Ca2+, but not in Ca2+ free medium. This result s uggested that Sit-G increases the fluidity of the mucosal membrane and faci litates Ca2+ influx from extracellular sources. In conclusion, a possible e xplanation for SG and Sit-G to promote drug absorption: is that they may af fect both paracellular pathway and transcellular pathways caused by pertuba tion of lipid. (C) 2000 Elsevier Science B.V. All rights reserved.