Advancing Darunavir Delivery: Nanoformulation strategies and innovations in HIV therapy.

Darunavir, a nonpeptidic protease inhibitor, remains a cornerstone of antiretroviral therapy due to its potent activity against wild-type HIV. However, its poor aqueous solubility and limited oral bioavailability, characteristic of Biopharmaceutical Classification System (BCS) Class II drugs, restrict therapeutic efficacy, with an absorption rate of only 37%. To address these pharmacokinetic limitations, nanotechnology-based strategies have been explored to enhance drug solubility, systemic exposure, and targeted tissue distribution. This review critically examines the potential of nanocarrier-based formulations, including solid lipid nanoparticles, supersaturated self-nanoemulsifying drug delivery systems, lipid nanoemulsions, poly(lactic-co-glycolic acid) nanoparticles, and cubosomes, in optimizing darunavir pharmacokinetics. These approaches have demonstrated improved bioavailability, sustained drug release, lymphatic targeting, and enhanced blood-brain barrier penetration, offering promising avenues for optimizing HIV therapy while minimizing systemic toxicity. Further, this review discusses challenges associated with nanoformulation-based antiretroviral strategies, scalability, manufacturing challenges, potential toxicity, immunogenicity, long-term stability issues, and explores emerging innovations, such as multifunctional nanoparticles, targeted delivery platforms, and sustainable nanotechnology-based formulations. By systematically evaluating current advances, this analysis provides critical insights into overcoming bioavailability constraints and facilitating the clinical translation of nanocarrier-based antiretroviral therapies.