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 μm of either rhodamine 123 (R-123) or 5(6)-Carboxy-2',7' 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.

LanguageEnglish
Pages889-897
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

Keywords

  • caco-2
  • efflux
  • excipients
  • P-glycoprotein
  • surfacants

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 μm of either rhodamine 123 (R-123) or 5(6)-Carboxy-2',7' 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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author = "John Pollard and Ali Rajabi-Siahboomi and Badhan, {Raj K. S.} and Mohammed, {Afzal R.} and Yvonne Perrie",
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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

T2 - Journal of Pharmacy and Pharmacology

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.

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 μm of either rhodamine 123 (R-123) or 5(6)-Carboxy-2',7' 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 μm of either rhodamine 123 (R-123) or 5(6)-Carboxy-2',7' 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.

KW - caco-2

KW - efflux

KW - excipients

KW - P-glycoprotein

KW - surfacants

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DO - 10.1111/jphp.13072

M3 - Article

VL - 71

SP - 889

EP - 897

JO - Journal of Pharmacy and Pharmacology

JF - Journal of Pharmacy and Pharmacology

SN - 0022-3573

IS - 6

ER -