Tirumalasetty Phani Prasanth, Eley John G
Harrison School of Pharmacy, Auburn University, Auburn, Alabama 36849, USA.
J Pharm Sci. 2005 Feb;94(2):246-55. doi: 10.1002/jps.20234.
Dodecylmaltoside (DDM), an alkylglycoside showing tissue-permeability-enhancing properties, has been successful in improving nasal and ocular transport of poorly absorbed drugs. It was hypothesized that optimization of DDM concentration would improve the transport of insulin across epithelial monolayers without causing cell damage. Samples of markers and insulin were collected over a 6-h period and transepithelial electrical resistance was measured at concurrent time points to ascertain the effect of DDM on tight junctions. Samples were analyzed for lucifer yellow and insulin using reversed-phase high-performance liquid chromatography and for (3)[H]-mannitol by scintillation counting. A significant increase in the transport of markers and insulin was recorded in DDM-treated cells compared with controls. DDM enhanced the transport of markers and insulin in a concentration-dependent manner. Decreased transepithelial electrical resistance values confirmed that enhanced transport is caused by loosening of tight junctions. Cell recovery was >95% in 8 h indicating the potential of DDM as a penetration enhancer for clinical administration of insulin and other poorly absorbed drugs without causing cell damage.
十二烷基麦芽糖苷(DDM)是一种具有增强组织通透性特性的烷基糖苷,已成功改善了难吸收药物的鼻腔和眼部转运。据推测,优化DDM浓度可改善胰岛素跨上皮单层的转运,且不会造成细胞损伤。在6小时内收集标志物和胰岛素样本,并在同一时间点测量跨上皮电阻,以确定DDM对紧密连接的影响。使用反相高效液相色谱法分析样本中的荧光素黄和胰岛素,通过闪烁计数法分析样本中的[³H] - 甘露醇。与对照组相比,DDM处理的细胞中标志物和胰岛素的转运显著增加。DDM以浓度依赖的方式增强了标志物和胰岛素的转运。跨上皮电阻值降低证实了转运增强是由紧密连接的松动引起的。8小时内细胞回收率>95%,表明DDM作为胰岛素和其他难吸收药物临床给药的渗透促进剂具有潜力,且不会造成细胞损伤。