Objective 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. Methods 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 lM of either rhodamine 123 (R-123) or 5(6)-Carboxy-20,70 dichlorofluorescein diacetate as probes of ABCB1 and ABCC2, respectively. Key findings 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. Conclusion 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.
Bibliographical note© 2019 The Authors. Journal of Pharmacy and Pharmacology published by John Wiley & Sons Ltd on behalf of Royal Pharmaceutical Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Funding: BBSRC Case award (Grant number BB/J012750/1) and Colorcon.
Pollard, J., Rajabi-siahboomi, A., Badhan, R. K. S., Mohammed, A. R., & Perrie, Y. (2019). High-throughput screening of excipients with a biological effect: a kinetic study on the effects of surfactants on efflux-mediated transport. Journal of Pharmacy and Pharmacology, 71(6), 889-897. https://doi.org/10.1111/jphp.13072