Synergistic inhibition of HIV-1 by Nelfinavir and Epigallocatechin Gallate: A novel nanoemulsion-based therapeutic approach

Abstract

The integration of nanotechnology into antiretroviral drug delivery systems presents a promising avenue to address challenges posed by long-term antiretroviral therapies (ARTs), including poor bioavailability, drug-induced toxicity, and resistance. These limitations impact the therapeutic effectiveness and quality of life for individuals living with HIV. Nanodrug delivery systems, particularly nanoemulsions, have demonstrated potential in improving drug solubility, enhancing bioavailability, and minimizing systemic toxicity. Moreover, nanodrug platforms can target viral reservoirs, potentially reducing the emergence of drug-resistant strains—a significant challenge in anti-HIV treatment. This study evaluates the biological efficacy of a rosemary oil-based nanoemulsion loaded with Nelfinavir (NFV) and Epigallocatechin Gallate (EGCG), which demonstrated HIV-1 suppression at sub-CC₅₀ concentrations across two distinct cellular systems. The synergistic interaction between NFV and EGCG was confirmed through cellular assays, enzymatic studies, and molecular interaction analysis. In vitro experiments revealed that the NE-NFV-EGCG nanoemulsion exhibited enhanced HIV-1 inhibitory activity compared to pure NFV, highlighting a promising therapeutic synergy. The findings suggest that EGCG could be a valuable adjunct in NFV-based regimens for HIV management. Molecular interaction studies further confirmed the nanoemulsion's inhibitory potential against the HIV-1 protease enzyme. This study marks a significant advancement in HIV-1 treatment by documenting, for the first time, the synergistic inhibitory activity of NFV and EGCG. The novel nanoformulation offers improved oral bioavailability, minimal side effects, and enhanced therapeutic outcomes. Future studies are needed to optimize the formulation for clinical applications, including sustained drug release and drug transport mechanisms.