布洛芬/羟丙基-β-环糊精体系的Caco-2细胞转运研究

Transport research of ibuprofen/HP-β-CD system in the Caco-2 monolayer model

目的：考察羟丙基-β-环糊精（HP-β-CD）超分子体系对布洛芬细胞转运的影响。方法：运用相溶解度法考察超分子体的表观稳定常数（K）;运用Caco-2细胞模型考察各类超分子体中布洛芬的表观渗透系数（Papp）以及跨膜电阻（TEER）的变化。结果：随HP-β-CD的浓度增加,布洛芬的溶解度不断提高;在0%~5%HP-β-CD的范围内,布洛芬的表观渗透系数随HP-β-CD的浓度增加逐渐下降;布洛芬三元体系表观稳定常数的变化趋势与布洛芬的表观渗透系数变化趋势相反。结论：布洛芬的细胞转运与体系中HP-β-CD浓度、超分子体系的稳定常数有密切关系。HP-β-CD浓度升高可显著增加布洛芬的溶解度,但过量的HP-β-CD不利于布洛芬的渗透转运;布洛芬、HP-β-CD通过与适量泊洛沙姆188（Poloxamer 188）、聚山梨酯-80（Tween-80）、十二烷基硫酸钠（SDS）组成的三元体系,可影响布洛芬、HP-β-CD之间的相互作用,改善布洛芬的表观渗透系数。

Objective：To investigate the effect of HP-β-CD supramolecular system on the transportation of ibuprofen. Methods：The apparent stability constant （K） of supramolecular system was studied by phase-solubillty. Caco-2 cell model in vitro was applied to investigate the apparent permeability coefficient （Ppp） of ibuprofen in the supramolecular system. Then the change of transepithelial electrical resistance （TEER） was measured. Results： The solubility of ibuprofen increased significantly along with the increasing of HP-β-CD concentration. When the concentration of HP-β-CD increased from 0% to 5% ,the apparent permeability coefficient of ibuprofen decreased along with the increasing of HP-β-CD concentration. The apparent stability constant of ternary supramolecular system increased while the apparent permeability coefficient of ibuprofen in the ternary supramolecular system de- creased. Conclusion：There was close relationship among the transport characteristics of ibuprofen,the concentration of HP-β-CD and the apparent stability constant of supramolecular system. The HP-β-CD improved significantly the solubility of ibuprofen. But excessive HP-β-CD inhibited the permeability of ibuprofen. The Poloxamer 188,Tween-80 and SDS can formulate ternary supramolecular system with ibuprofen and HP-β-CD. Then the interaction between ibuprofen and HP-β-CD was influenced. The ternary supramolecular system can improve the P pp of ibuprofen.