Nakanishi K, Nadai T, Masada M, Miyajima K
Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.
Chem Pharm Bull (Tokyo). 1992 May;40(5):1252-6. doi: 10.1248/cpb.40.1252.
The effects of two kinds of cyclodextrins (CyDs), alpha- and beta-CyD, on biological membranes were investigated by measuring changes in the absorption of a non-absorbable drug, sulfanilic acid (SA), from the rat small intestine, using in situ and in vitro experiments. After pretreatment with a mucolytic agent, N-acetyl-L-cysteine (N-Ac), only beta-CyD increased the absorption of SA significantly compared to the absorption without pretreatment. The mechanism of the enhancing effect of CyDs on the absorption of SA was discussed. Almost no morphological change in the small intestine was observed by pretreatment with N-Ac alone, N-Ac or alpha- or beta-CyD combinations. The liberation of membrane components differed among the CyDs, e.g., alpha-CyD selectively released phospholipid while beta-CyD released mainly cholesterol from the intestinal membrane. It is suggested that the interaction of membrane components with CyDs may be at least partly responsible for the enhanced absorption of SA. Moreover it was found from in vitro electrophysiological experiment, that the alteration in enhanced permeability caused by beta-CyD occurred primarily in the transcellular pathways, rather than in the paracellular pathways of the small intestine. These results suggest that the enhancement of intestinal absorption by beta-CyD, after removal of the mucin layer from the intestinal surface, is due to the interaction between the membrane components and CyD. This interaction would induce disorder in cell membrane lipid, resulting in the increased permeability of the transcellular route.
通过原位和体外实验，测量大鼠小肠中不可吸收药物磺胺酸（SA）的吸收变化，研究了两种环糊精（CyD），即α-环糊精和β-环糊精对生物膜的影响。在用粘液溶解剂N-乙酰-L-半胱氨酸（N-Ac）预处理后，与未预处理相比，只有β-环糊精显著增加了SA的吸收。讨论了环糊精对SA吸收增强作用的机制。单独用N-Ac、N-Ac与α-或β-环糊精组合预处理后，小肠几乎未观察到形态变化。不同环糊精对膜成分的释放情况不同，例如，α-环糊精选择性释放磷脂，而β-环糊精主要从肠膜中释放胆固醇。提示膜成分与环糊精的相互作用可能至少部分是SA吸收增强的原因。此外，从体外电生理实验发现，β-环糊精引起的通透性增强主要发生在小肠的跨细胞途径，而非细胞旁途径。这些结果表明，从肠表面去除粘蛋白层后，β-环糊精增强肠吸收是由于膜成分与环糊精之间的相互作用。这种相互作用会导致细胞膜脂质紊乱，从而使跨细胞途径的通透性增加。
