du Toit Trizel, Malan Maides M, Lemmer Hendrik J R, Gouws Chrisna, Aucamp Marique E, Breytenbach Wilma J, Hamman Josias H
Faculty of Health Sciences, Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa.
Statistical Consultation Services, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa.
Eur J Drug Metab Pharmacokinet. 2016 Oct;41(5):575-86. doi: 10.1007/s13318-015-0280-7.
Currently, macromolecular drugs such as proteins are mainly administered by means of injections due to their low intestinal epithelial permeability and poor stability in the gastrointestinal tract. This study investigated binary combinations of chemical drug absorption enhancers to determine if synergistic drug absorption enhancement effects exist. Aloe vera, Aloe ferox and Aloe marlothii leaf gel materials, as well as with N-trimethyl chitosan chloride (TMC), were combined in different ratios and their effects on the transepithelial electrical resistance (TEER), as well as the transport of FITC-dextran across Caco-2 cell monolayers, were measured. The isobole method was applied to determine the type of interaction that exists between the absorption enhancers combinations. The TEER results showed synergism existed for the combinations between A. vera and A. marlothii, A. marlothii and A. ferox as well as A. vera and TMC. Antagonism interactions also occurred and can probably be explained by chemical reactions between the chemical permeation enhancers, such as complex formation. In terms of FITC-dextran transport, synergism was found for combinations between A. vera and A. marlothii, A. marlothii and A. ferox, A. vera and TMC, A. ferox and TMC and A. marlothii and TMC, whereas antagonism was observed for A. vera and A. ferox. The combinations where synergism was obtained have the potential to be used as effective drug absorption enhancers at lower concentrations compared to the single components.
目前，蛋白质等大分子药物主要通过注射给药，因为它们在肠道上皮的通透性较低，且在胃肠道中的稳定性较差。本研究调查了化学药物吸收促进剂的二元组合，以确定是否存在协同的药物吸收增强作用。将库拉索芦荟、好望角芦荟和莫氏芦荟叶凝胶材料，以及与氯化N-三甲基壳聚糖（TMC）以不同比例混合，并测量它们对跨上皮电阻（TEER）以及FITC-葡聚糖跨Caco-2细胞单层转运的影响。采用等效线法确定吸收促进剂组合之间存在的相互作用类型。TEER结果表明，库拉索芦荟与莫氏芦荟、莫氏芦荟与好望角芦荟以及库拉索芦荟与TMC之间的组合存在协同作用。也发生了拮抗相互作用，这可能可以通过化学渗透促进剂之间的化学反应来解释，例如复合物的形成。就FITC-葡聚糖转运而言，发现库拉索芦荟与莫氏芦荟、莫氏芦荟与好望角芦荟、库拉索芦荟与TMC、好望角芦荟与TMC以及莫氏芦荟与TMC之间的组合具有协同作用，而库拉索芦荟与好望角芦荟之间则观察到拮抗作用。与单一成分相比，获得协同作用的组合有可能在较低浓度下用作有效的药物吸收促进剂。
