Maitani Y, Nakamura K, Suenaga H, Kamata K, Takayama K, Nagai T
Department of Pharmaceutics, Hoshi University, Shinagawa, Tokyo, Japan.
Int J Pharm. 2000 Apr 25;200(1):17-26. doi: 10.1016/s0378-5173(99)00470-6.
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.
本研究的目的是阐明大豆源甾醇糖苷（SG）及其主要成分β-谷甾醇β-D-葡萄糖苷（Sit-G）作为鼻腔吸收促进剂的效率。维拉帕米与SG和Sit-G经鼻腔给药后的生物利用度（分别为60.4%和90.7%）高于与乳糖联合给药后的生物利用度（39.8%）。显然，SG和Sit-G促进了维拉帕米经鼻黏膜的吸收。为阐明其机制，我们通过与SG、Sit-G、油酸、大豆源甾醇和β-谷甾醇孵育来测量脂质体中钙黄绿素的泄漏，以研究跨细胞吸收，并通过Sit-G测量细胞内Ca2+浓度（[Ca2+]i）的变化，以分析细胞旁吸收。增强剂诱导的大量钙黄绿素泄漏与鼻腔给药后维拉帕米和胰岛素生物利用度的提高一致（油酸＜SG＜Sit-G）。此外，Sit-G在含Ca2+的培养基中增加了[Ca2+]i，但在无Ca2+的培养基中未增加。该结果表明，Sit-G增加了黏膜膜的流动性，并促进了细胞外Ca2+的内流。总之，SG和Sit-G促进药物吸收的一个可能解释是，它们可能通过干扰脂质影响细胞旁途径和跨细胞途径。
