Labrasol, as a non-ionic surfactant, can enhance the permeation and absorption of drugs, and is extensively used in topical, transdermal, and oral pharmaceutical preparations as an emulsifier and absorption enhancer. ...Labrasol, as a non-ionic surfactant, can enhance the permeation and absorption of drugs, and is extensively used in topical, transdermal, and oral pharmaceutical preparations as an emulsifier and absorption enhancer. Recent studies in our laboratory have indicated that labrasol has a strong absorption enhancing effect on different types of drugs in vitro and in vivo. This study was performed to further elucidate the action mechanism of labrasol on the corneal penetration. In this research, the fluorescein sodium, a marker of passive paracellular transport of tight junction, was selected as the model drug to assess the effect of labrasol on in vitro corneal permeability. To investigate the continuous and real-time influence of labrasol on the membrane permeability and integrity, the Ussing chamber system was applied to monitor the electrophysiological parameters. And, furthermore, we elucidated the effect of labrasol on excised cornea at the molecular level by application of RT-PCR, Western blot, and immunohistochemical staining. The results indicated that labrasol obviously enhance the transcorneal permeability of fluorescein sodium, and the enhancement was realized by interacting with and down-regulating the associated proteins, such as Factin, claudin-1 and β-catenin, which were contributed to cell-cell connections, respectively.展开更多
目的采用Box-Behnken响应面法优化白藜芦醇(resveratrol)-辛酸癸酸聚乙二醇甘油酯(Labrasol)/泊洛沙姆407(P407)混合胶束(Res-Labrasol/P407-MM)的处方工艺,并考察其体外特征。方法HPLC法测定白藜芦醇含量。薄膜分散-探头超声法制备Res-...目的采用Box-Behnken响应面法优化白藜芦醇(resveratrol)-辛酸癸酸聚乙二醇甘油酯(Labrasol)/泊洛沙姆407(P407)混合胶束(Res-Labrasol/P407-MM)的处方工艺,并考察其体外特征。方法HPLC法测定白藜芦醇含量。薄膜分散-探头超声法制备Res-Labrasol/P407-MM。在单因素实验结果的基础上,以投药量、水化体积和水化温度为考察因素,胶束样品的质量浓度和药物沉降率为评价指标,采用Box-Behnken响应面法优化处方,并对最优处方制备的胶束进行外观形态、粒径和体外释放行为评价。结果最佳处方工艺为白藜芦醇投药量28 mg,水化体积9 m L,水化温度40℃,在此条件下测得白藜芦醇平均载药量为(11.62±0.20)%、平均包封率为(93.96±1.83)%、胶束平均粒径为(69.00±1.58)nm,平均Zeta电位为(-21.25±0.18)m V。样品质量浓度和沉降率的实测值与预测值偏差较小,RSD<5.5%。结论Box-Behnken响应面法预测性良好,可以用于优化Res-Labrasol/P407-MM的处方工艺。制备的混合胶束包封率高,粒径小,分布均匀,缓释效果明显。展开更多
文摘[目的]研究表面活性剂辛酸癸酸聚乙二醇甘油酯(Labrasol)对羟基红花黄色素A(hydroxysafflor yellow A,HSYA)口服生物利用度的影响及其跨膜转运机理。[方法]24只SPF级SD大鼠随机分成正常对照组、Labrasol低剂量组、Labrasol中剂量组、Labrasol高剂量组(n=6),各组灌胃HSYA50mg以及不同浓度的Labrasol。各组大鼠灌胃给药后,用HPLC测定HSYA的血药浓度,并用人结肠癌细胞(Caco-2)药物转运模型探究Labrasol对HSYA跨膜转运影响的机理。[结果]Labrasol能显著提高HSYA血药浓度,当配方中Labrasol为20%时,HSYA达到最大的口服生物利用度,8h内药时曲线面积(area under the curve,AUC)为101.425μg·h·m L-1,是口服HSYA水溶液的3.26倍;在Labrasol的作用下,Caco-2药物转运模型从基底侧(basolateral side,BL)到顶侧(apical side,AP)明显小于AP到BL的转运速率,Labrasol对HSYA跨膜转运的影响与P-糖蛋白(P-glycoprotein,P-gp)抑制剂维拉帕米相比,作用效果相当。[结论]Labrasol能显著提高HSYA口服生物利用度;Labrasol可能通过抑制存在于肠黏膜的P-gp活性而增加HSYA的跨膜转运能力。
文摘Labrasol, as a non-ionic surfactant, can enhance the permeation and absorption of drugs, and is extensively used in topical, transdermal, and oral pharmaceutical preparations as an emulsifier and absorption enhancer. Recent studies in our laboratory have indicated that labrasol has a strong absorption enhancing effect on different types of drugs in vitro and in vivo. This study was performed to further elucidate the action mechanism of labrasol on the corneal penetration. In this research, the fluorescein sodium, a marker of passive paracellular transport of tight junction, was selected as the model drug to assess the effect of labrasol on in vitro corneal permeability. To investigate the continuous and real-time influence of labrasol on the membrane permeability and integrity, the Ussing chamber system was applied to monitor the electrophysiological parameters. And, furthermore, we elucidated the effect of labrasol on excised cornea at the molecular level by application of RT-PCR, Western blot, and immunohistochemical staining. The results indicated that labrasol obviously enhance the transcorneal permeability of fluorescein sodium, and the enhancement was realized by interacting with and down-regulating the associated proteins, such as Factin, claudin-1 and β-catenin, which were contributed to cell-cell connections, respectively.
文摘目的采用Box-Behnken响应面法优化白藜芦醇(resveratrol)-辛酸癸酸聚乙二醇甘油酯(Labrasol)/泊洛沙姆407(P407)混合胶束(Res-Labrasol/P407-MM)的处方工艺,并考察其体外特征。方法HPLC法测定白藜芦醇含量。薄膜分散-探头超声法制备Res-Labrasol/P407-MM。在单因素实验结果的基础上,以投药量、水化体积和水化温度为考察因素,胶束样品的质量浓度和药物沉降率为评价指标,采用Box-Behnken响应面法优化处方,并对最优处方制备的胶束进行外观形态、粒径和体外释放行为评价。结果最佳处方工艺为白藜芦醇投药量28 mg,水化体积9 m L,水化温度40℃,在此条件下测得白藜芦醇平均载药量为(11.62±0.20)%、平均包封率为(93.96±1.83)%、胶束平均粒径为(69.00±1.58)nm,平均Zeta电位为(-21.25±0.18)m V。样品质量浓度和沉降率的实测值与预测值偏差较小,RSD<5.5%。结论Box-Behnken响应面法预测性良好,可以用于优化Res-Labrasol/P407-MM的处方工艺。制备的混合胶束包封率高,粒径小,分布均匀,缓释效果明显。
