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 human immunodeficiency virus (HIV). However, its poor aqueous solubility and limited oral bioavailability, characteristic of Biopharmaceutical Classification System 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.