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

Pollard, John and Rajabi-Siahboomi, Ali and Badhan, Raj K. S. and Mohammed, Afzal R. and Perrie, Yvonne (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). pp. 889-897. ISSN 0022-3573 (https://doi.org/10.1111/jphp.13072)

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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.

  • Item type:Article
    ID code:67097
    Dates:
    Date
    Event
    1 June 2019
    Published
    19 February 2019
    Published Online
    12 January 2019
    Accepted
    Notes:© 2019 The Authors. Journal of Pharmacy and Pharmacology published by John Wiley & Sons Ltd on behalf of Royal Pharmaceutical Society.
    Keywords:caco-2, efflux, excipients, P-glycoprotein, surfacants, Pharmacy and materia medica, Pharmacology, Toxicology and Pharmaceutics(all)
    Subjects:Medicine > Pharmacy and materia medica
    Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
    Depositing user: Pure Administrator
    Date deposited:26 Feb 2019 12:56
    Last modified:25 May 2023 10:22
    URI:https://strathprints.strath.ac.uk/id/eprint/67097
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