The present study aimed to develop a nanoemulsion loaded with dolutegravir (DTG) and Epigallocatechin Gallate (EGCG) to achieve a combined and synergistic effect for improved oral delivery, facilitating more effective management of NeuroAIDS. Thyme oil was chosen as the oil, tween 80 as the surfactant, and transcutol®HP as the co-surfactant following extensive screening of experiments. The nanoemulsion was fabricated using the ultrasonication technique and optimization was performed using a Central Composite Rotatable Design (CCRD) to attain the best formulation following parameters like droplet size, polydispersity index (PDI), zeta potential, % transmittance, pH, refractive index, viscosity and conductivity of the optimized nanoemulsion, which were found to be 45.36 nm, 0.2462, −6.226 mV, 96.30 ± 0.20 %, 6.84 ± 0.32, 1.70 ± 0.12, 31.17 ± 0.21 mPas, and 0.217 ± 0.002 mS/cm, respectively. The developed formulation was thoroughly characterized and investigated through various in vitro studies, demonstrating enhanced drug release. The nanoemulsion showcased a spherical and globular nature of the droplets, resulting in improved drug bioavailability compared to the pure drug. In conclusion, the DTG and EGCG-loaded nanoemulsion formulation offers a promising approach for achieving a combined anti-HIV effect, with potential for effective NeuroAIDS management. Future investigations will focus on validating the anti-HIV-1 properties of this nanoemulsion formulation, employing in-depth mechanistic analysis through in vitro preclinical studies, to further elucidate their synergistic effects and optimize therapeutic potential against HIV-1 infection.
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