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.
| Language | English |
|---|---|
| Pages | 889-897 |
| Number of pages | 9 |
| Journal | Journal of Pharmacy and Pharmacology |
| Volume | 71 |
| Issue number | 6 |
| Early online date | 19 Feb 2019 |
| DOIs | |
| Publication status | Published - 1 Jun 2019 |
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Keywords
- caco-2
- efflux
- excipients
- P-glycoprotein
- surfacants
Cite this
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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 journal › Article
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
U2 - 10.1111/jphp.13072
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 -