Tirumalasetty Phani Prasanth, Eley John G
Corium International, Inc., Redwood City, California, USA.
J Pharm Pharm Sci. 2006;9(1):32-9.
To evaluate the permeability enhancing effects of octylglucoside (OG) for molecules with poor absorption such as insulin by in vitro cell models.
Transepithelial electrical resistance (TEER) was monitored to ensure monolayer integrity. Permeability was ascertained using paracellular markers. Markers and insulin were dissolved in Hanks balanced salt solution and placed on the apical side of the cells in Transwell(c) plates and allowed to diffuse under sink conditions.
The effect of OG on the permeability of molecules across both monolayers was concentration and time dependent. Enhanced transport of the three molecules was observed across both monolayers treated with OG as compared to untreated monolayers. The effects of OG were reversible at low concentrations but there was permanent damage to cells at higher concentrations. Absorption enhancement was greater across T-84 monolayers compared to Caco-2 monolayers.
The results indicate OG has potential as a permeability enhancer for poorly absorbed drugs with no significant damage to monolayers at low concentrations. Immediate attenuation in TEER upon exposure to OG indicates that permeability enhancing effects were likely to be associated with modulation of tight junctions suggesting the involvement of paracellular transport.
通过体外细胞模型评估辛基葡糖苷（OG）对胰岛素等吸收较差分子的渗透增强作用。
监测跨上皮电阻（TEER）以确保单层细胞的完整性。使用细胞旁标记物确定渗透性。将标记物和胰岛素溶解在汉克斯平衡盐溶液中，置于Transwell（c）板中细胞的顶端，在漏槽条件下使其扩散。
OG对分子跨两个单层的渗透性的影响呈浓度和时间依赖性。与未处理的单层相比，在经OG处理的两个单层中均观察到三种分子的转运增强。OG在低浓度下的作用是可逆的，但在高浓度下会对细胞造成永久性损伤。与Caco-2单层相比，T-84单层的吸收增强更大。
结果表明，OG有潜力作为吸收较差药物的渗透增强剂，在低浓度下对单层细胞无明显损伤。暴露于OG后TEER立即衰减表明，渗透增强作用可能与紧密连接的调节有关，提示涉及细胞旁转运。
