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 sterylglucoside (SG) and its main component beta-sitosterol beta-D-glucoside (Sit-G), as nasal absorption enhancers. Nasal administration of verapamil with SG and Sit-G showed the higher bioavailabilities (60.4 and 90.7%, respectively) than that with lactose (39.8%). It was clear that SG and Sit-G promoted the absorption of verapamil through nasal mucosa. To elucidate the mechanism, we measured the calcein leakage from liposomes by incubation with SG, Sit-G, oleic acid, soybean-derived sterol, and beta-sitosterol to investigate transcellular absorption and measured the changes in intracellular Ca2+ concentrations ([Ca2+]i) by Sit-G to analyze paracellular absorption. The 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 suggested that Sit-G increases the fluidity of the mucosal membrane and facilitates Ca2+ influx from extracellular sources. In conclusion, a possible explanation for SG and Sit-G to promote drug absorption, is that they may affect both paracellular pathway and transcellular pathways caused by pertubation of lipid.
Maitani
Y
Y
Department of Pharmaceutics, Hoshi University, Shinagawa, Tokyo, Japan. yoshie@hoshi.acjp
Nakamura
K
K
Suenaga
H
H
Kamata
K
K
Takayama
K
K
Nagai
T
T
D000042:Absorption / Q000187:drug effects; D000281:Administration, Intranasal; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics; D002782:Cholestenes / Q000737:chemistry*; D004337:Drug Carriers; D005452:Fluoresceins / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D007328:Insulin / Q000008:administration & dosage / Q000493:pharmacokinetics; D008081:Liposomes; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism*; D011208:Powders; D011817:Rabbits; D012855:Sitosterols / Q000737:chemistry*; D014700:Verapamil / Q000008:administration & dosage / Q000493:pharmacokinetics
D002121:Calcium Channel Blockers; D002782:Cholestenes; D004337:Drug Carriers; D005452:Fluoresceins; D007004:Hypoglycemic Agents; D007328:Insulin; D008081:Liposomes; D011208:Powders; D012855:Sitosterols; C096056:soy derived sterylglucoside mixture; D014700:Verapamil; D002118:Calcium; C011015:lyoniside; C007740:fluorexon