Aston Pharmacy School, School of Life and Health Sciences, Aston University, Birmingham, UK.
Colorcon, Harleysville, PA, USA.
J Pharm Pharmacol. 2019 Jun;71(6):889-897. doi: 10.1111/jphp.13072. Epub 2019 Feb 19.
In this study, we develop and apply a high-throughput screening protocol to investigate the activity of non-ionic surfactants, with a broad range of hydrophilic-lipophilic balance values, against ABCB1-mediated efflux transport and ABCC2-mediated efflux transport.
Caco-2 cells were grown for 7 days in 96-well plates, then washed and incubated with the test materials for 2 h in the presence of 2.5 μm of either rhodamine 123 (R-123) or 5(6)-Carboxy-2',7' dichlorofluorescein diacetate as probes of ABCB1 and ABCC2, respectively.
Of the surfactants tested, no activity against ABCC2 was detected and all surfactants showing efficacy against ABCB1 had a HLB value of 22 or below. Inhibition of ABCB1 was seen in the order of efficacy to be poloxamer 335 > poloxamer 40 > Crovol A-70 > Myrj S-40 > poloxamer 184 > poloxamer 182 > Etocas 40 > Tween 20 > Etocas 29 > Tween 80 > Acconon C-44 > Span 20. With regard to this inhibition, the distribution of hydrophilic regions is more important than the HLB value.
This work demonstrates a high-throughput protocol for detecting materials that can modulate ABCB1-mediated efflux. These surfactants could be exploited to improve oral delivery of drugs prone to efflux.
在这项研究中，我们开发并应用了一种高通量筛选方案，以研究具有广泛亲水亲脂平衡值的非离子表面活性剂对 ABCB1 介导的外排转运和 ABCC2 介导的外排转运的活性。
Caco-2 细胞在 96 孔板中培养 7 天，然后用测试材料洗涤并孵育 2 小时，在存在 2.5 μm 的 rhodamine 123（R-123）或 5(6)-Carboxy-2',7' dichlorofluorescein diacetate 的情况下，分别作为 ABCB1 和 ABCC2 的探针。
在所测试的表面活性剂中，未检测到对 ABCC2 的活性，所有对 ABCB1 有效的表面活性剂的 HLB 值均为 22 或以下。ABCB1 的抑制作用按功效顺序为泊洛沙姆 335>泊洛沙姆 40>克罗沃 A-70>Myrij S-40>泊洛沙姆 184>泊洛沙姆 182>乙氧基卡斯 40>吐温 20>乙氧基卡斯 29>吐温 80>Acconon C-44>Span 20。关于这种抑制作用，亲水区域的分布比 HLB 值更重要。
这项工作展示了一种用于检测可调节 ABCB1 介导的外排的物质的高通量方案。这些表面活性剂可以被利用来改善易外排的药物的口服递送。
