High-throughput screening of excipients with a biological effect: a kinetic study on the effects of surfactants on efflux-mediated transport

John Pollard, Ali Rajabi-siahboomi, Raj K. S. Badhan, Afzal R. Mohammed, Yvonne Perrie

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
Pages (from-to)889-897
Number of pages9
JournalJournal of Pharmacy and Pharmacology
Volume71
Issue number6
Early online date19 Feb 2019
DOIs
Publication statusPublished - 1 Jun 2019

Fingerprint

Poloxamer
Excipients
Surface-Active Agents
Polysorbates
Rhodamine 123
Caco-2 Cells
Pharmaceutical Preparations

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.

Keywords

  • Caco-2
  • efflux
  • excipients
  • P-glycoprotein
  • surfactants

Cite this

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title = "High-throughput screening of excipients with a biological effect: a kinetic study on the effects of surfactants on efflux-mediated transport",
abstract = "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.",
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High-throughput screening of excipients with a biological effect: a kinetic study on the effects of surfactants on efflux-mediated transport. / Pollard, John; Rajabi-siahboomi, Ali; Badhan, Raj K. S.; Mohammed, Afzal R.; Perrie, Yvonne.

In: Journal of Pharmacy and Pharmacology, Vol. 71, No. 6, 01.06.2019, p. 889-897.

Research output: Contribution to journalArticle

TY - JOUR

T1 - High-throughput screening of excipients with a biological effect: a kinetic study on the effects of surfactants on efflux-mediated transport

AU - Pollard, John

AU - Rajabi-siahboomi, Ali

AU - Badhan, Raj K. S.

AU - Mohammed, Afzal R.

AU - Perrie, Yvonne

N1 - © 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.

PY - 2019/6/1

Y1 - 2019/6/1

N2 - 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.

AB - 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.

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KW - excipients

KW - P-glycoprotein

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