Comprehensive insights into herbal P-glycoprotein inhibitors and nanoformulations for improving anti-retroviral therapy efficacy

Abstract

The worldwide HIV cases were 39.0 million (33.1–45.7 million) in 2022. Due to genetic variations, HIV-1 is more easily transmitted than HIV-2 and favours CD4 + T cells and macrophages, producing AIDS. Conventional HIV drug therapy has many drawbacks, including adherence issues leading to resistance, side effects that lower life quality, drug interactions, high costs limiting global access, inability to eliminate viral reservoirs, chronicity requiring lifelong treatment, emerging toxicities, and a focus on managing infections. Conventional dosage forms have bioavailability issues due to intestinal P-glycoprotein (P-gp) efflux, which can reduce anti-retroviral drug efficacy and lead to resistance. Use of phyto-constituents with P-gp regulating actions has great benefits for semi-synthetic modification to create formulations with greater bioavailability and reduced toxicity, which improves drug effectiveness. Lipid-based nanocarriers, solid lipid nanoparticles, nanostructured lipid carriers, polymer-based nanocarriers, and inorganic nanoparticles may inhibit P-gp efflux. Employing potent P-gp inhibitors within nanocarriers as a Trojan horse approach can enhance the intracellular accumulation of anti-retroviral drugs (ARDs), which are substrates for efflux transporters. This technique increases oral bioavailability and offers lower-dose options, boosting HIV patient compliance and lowering costs. Molecular docking of the inhibitor with P-gp may anticipate optimum binding and function, allowing drug efflux to be minimised.

Graphical Abstract

Keywords:

• HIV
• P-glycoprotein
• efflux
• bioavailability
• herbal
• molecular docking
• nanocarrier

Authors’ contributions

The First author PJ and Co-author SP performed Data curation, Formal analysis, Investigation, Methodology and Writing -original draft; Co-author PP executed Supervision, Conceptualisation, Writing - review & editing; Co-author SS contributed in review; Corresponding author KA was involved in Conceptualisation, Project administration; Resources; Supervision; Validation; Visualisation and Writing - review & editing.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.