High-throughput screening of excipients with a biological effect

In this study, we develop and apply a high-throughput screening pro- tocol 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 rho- damine 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. Download full article here: high-throughput-screening-of-excipients-with-a-biological-effect.pdf or continue reading this JPP article on onlinelibrary.wiley.com