Nanotechnology-Based Delivery Systems for Quercetin and Curcumin: Formulation Strategies, Bioavailability Enhancement, Therapeutic Applications, and Translational Challenges

Abstract

Quercetin and curcumin are extensively investigated plant-derived polyphenolic bioactives with antioxidant, anti-inflammatory, anticancer, and cytoprotective activities, but their translation into reproducible therapeutic products is restricted by unfavorable biopharmaceutical properties. Quercetin is a flavonol with limited aqueous solubility, extensive intestinal and hepatic conjugation, and formulation-dependent absorption, whereas curcumin is a diarylheptanoid curcuminoid - not a flavonoid - characterized by very low water solubility, chemical instability, rapid metabolism, and low systemic exposure after conventional oral dosing. Nanotechnology-based delivery systems have therefore been explored to increase apparent solubility, protect the payload from degradation, improve mucosal transport and cellular uptake, prolong residence or circulation, and enable controlled or targeted release. This review critically compares nanocarriers developed for quercetin and curcumin, including polymeric nanoparticles, liposomes, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, self-emulsifying systems, micelles, nanocrystals, nanosuspensions, chitosan-based systems, and selected hybrid platforms. Particular attention is given to formulation composition, manufacturing approaches, critical quality attributes, pharmacokinetic evidence, therapeutic applications, and the distinction between preclinical promise and demonstrated clinical benefit. Human pharmacokinetic studies show that formulation can substantially alter systemic exposure for both compounds; however, cross-study fold-changes are not directly comparable because dose, analytical treatment of conjugated metabolites, reference formulations, and study design differ. Translation is additionally limited by scale-up, batch reproducibility, nanocarrier safety, long-term stability, regulatory characterization, and oral-product contamination control. A quality-by-design framework linking material attributes and process parameters to particle size distribution, drug loading, release, stability, and in vivo performance is proposed as a more defensible route toward clinically relevant products. Overall, nanotechnology can address important delivery barriers for quercetin and curcumin, but improved bioavailability should be treated as an enabling pharmacokinetic outcome rather than proof of therapeutic efficacy.