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Non-ionic Surfactants as a P-Glycoprotein(P-gp) Efflux Inhibitor for Optimal Drug Delivery—A Concise Outlook

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Abstract

Significant research efforts have been devoted to unraveling the mystery of P-glycoprotein(P-gp) in drug delivery applications. The efflux membrane transporter P-gp is widely distributed in the body and accountable for restricting drug absorption and bioavailability. For these reasons, it is the primary cause of developing multidrug resistance (MDR) in most drug delivery applications. Therefore, P-gp inhibitors must be explored to address MDR and the low bioavailability of therapeutic substrates. Several experimental models in kinetics and dynamic studies identified the sensitivity of drug molecules and excipients as a P-gp inhibitor. In this review, we aimed to emphasize nonionic surface-active agents for effective reversal of P-gp inhibition. As it is inert, non-toxic, noncharged, and quickly reaching the cytosolic lipid membrane (the point of contact with P-gp efflux protein) enables it to be more efficient as P-gp inhibitors. Moreover, nonionic surfactant improves drug absorption and bioavailability through the various mechanism, involving (i) association of drug with surfactant improves solubilization, facilitating its cell penetration and absorption; (ii) weakening the lateral membrane packing density, facilitating the passive drug influx; and (iii) inhibition of the ATP binding cassette of transporter P-glycoprotein. The application of nonionic surfactant as P-gp inhibitors is well established and supported by various experiments. Altogether, herein, we have primarily focused on various nonionic surfactants and their development strategies to conquer the MDR-causing effects of P-gp efflux protein in drug delivery.

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Authors and Affiliations

  1. Uka Tarsadia University, Maliba Pharmacy College, Gopal-Vidyanagar Campus, Surat, 394350, India

    Sachin Rathod & Jayant Sarolia

  2. Parul University, Parul Institute of Pharmacy and Research, Vadodara, 391760, India

    Sachin Rathod & Heta Desai

  3. Shri Dhanvantary Pharmacy College, Surat, 394110, India

    Rahul Patil

  4. Vadodara, India

    Jayant Sarolia

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  1. Sachin Rathod
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  2. Heta Desai
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  3. Rahul Patil
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  4. Jayant Sarolia
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Sachin Rathod: writing—original draft preparation and editing; Heta desai: writing—original draft. Rahul Patil: reviewing and editing; Jayant Sarolia: writing—review and editing.

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Correspondence to Jayant Sarolia.

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Rathod, S., Desai, H., Patil, R. et al. Non-ionic Surfactants as a P-Glycoprotein(P-gp) Efflux Inhibitor for Optimal Drug Delivery—A Concise Outlook. AAPS PharmSciTech 23, 55 (2022). https://doi.org/10.1208/s12249-022-02211-1

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