Nanotechnology-Enhanced Delivery and Bioactivity of Dietary Flavonoids: Overcoming Bioavailability Barriers for Targeted Antimicrobial and Antiviral Therapies-A Comprehensive Review

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Abstract: Flavonoids are a class of naturally occurring compounds primarily present in plants and are also part of some of the byproducts of certain insects’ metabolites, such as propolis. Given the growing burden of infectious diseases and the urgent need for more effective therapeutic options, advancing flavonoid-based interventions is of prime clinical significance. These compounds possess unique chemical characteristics and exhibit pronounced biological activities, including antioxidant, anti-inflammatory, antiviral, immunomodulatory, and antibacterial, making the class a potent contender for managing certain health concerns, including health issues arising out of pandemic situations. However, limitations involving low aqueous solubility, less oral bioavailability, fast metabolism, structural instability, and limited tissue targeting have restricted their clinical applications as therapeutic agents. In this context, nanotechnology offers feasible remediation to overcome these shortcomings by enhancing solubility, absorption, transitional stability, and controlled and sustained release, as well as enhanced on-site bioavailability and effective therapeutic control that transforms into increased biological activity. The current overview encompasses literature information collected from the database platforms of PubMed, Google Scholar, ScienceDirect, Scopus, and Web of Science, with the particular focus on studies published in the last decade (2015– 2025). Information relating to nanotechnology-enabled flavonoid delivery covering polymeric and lipid nanoencapsulates, nanoemulsions, nanocrystals, liposomes, solid lipid nanoparticles (SLNPs), nanostructured lipid carriers, metallic NPs, and nanofibers has been assessed and analyzed. These nanosystems and complex delivery platforms have demonstrated improvements in flavonoids’ solubility, cellular uptake, circulation time, and stability and have facilitated targeted/sustained release of the payload to the sites of action, ie, infections and inflammations. Additionally, the environmentally benign green synthetic approaches for constituent flavonoids and their formulations emphasized the roles in enhancing the safety, toxicity reduction, stability, and sustainable use. Although preclinical studies have produced encouraging therapeutic results, the clinical translation requires standardized flavonoid sources, reproducible protocols, scaling-up formulation methods, comprehensive physicochemical characterization, toxicity evaluations, and pharmacokinetic studies with rigorously designed clinical trials. Keywords: flavonoids, nanotechnology, nanocarriers, antimicrobial, antiviral, preclinical, drug delivery