Nutraceuticals such as curcumin, resveratrol, lycopene, lutein, and coenzyme Q10 pos-sess strong antioxidant and anti-inflammatory activities but their practical use is hin-dered by poor solubility and bioavailability. Traditional nanocarriers like liposomes, nanoemulsions, and polymeric nanoparticles often rely on surfactants and synthetic or-ganic solvents that limit safety, scalability, and regulatory acceptance. The present study evaluated the Facilitated Self-Assembling Technology (FAST) platform as a clean-label al-ternative for generating bioavailable nutraceutical nanoparticles. Using only food-grade facilitating medium, FAST enabled spontaneous formation of stable, amorphous nano-particles with strong negative surface charge and high colloidal stability. Hybrid nano-particles combining epigallocatechin-3-gallate-palmitates (EC16), curcumin, and resvera-trol further improved surface charge, reduced size range, and exhibited enhanced stability under simulated gastric conditions. All formulations demonstrated excellent biocompati-bility in XTT assays, with no reduction in viability compared to control. Fluorescent im-aging of EC16/Cy5 fluorescent hybrid nanoparticles confirmed nanoparticle–cell surface interactions without cytotoxicity. Compared with chemical conjugation and lipid-based nanoencapsulation, FAST offered faster, surfactant-free, and energy-efficient production, fully compliant with FDA generally recognized as safe (GRAS) standards. These results support the FAST platform as an efficient, economical, and scalable nanotechnology for next-generation functional beverages and oral nutraceutical delivery systems that meet both regulatory and consumer demands for natural, sustainable innovation.

Poor aqueous solubility remains a major barrier to the development, repurposing, and improved delivery of many clinically important small-molecule drugs. This problem is especially important for Biopharmaceutics Classification System (BCS) Class II drugs, in which intestinal permeability may be acceptable but dissolution and aqueous formulation compatibility limit absorption, formulation flexibility, and translational testing. Current formulation-enabling strategies, including solid dispersions, nanosuspensions, nanocrystals, lipid-based systems, cyclodextrin complexes, self-emulsifying systems, and polymer- or surfactant-stabilized particles, can improve drug dissolution and exposure, but these approaches often require drug-specific formulation optimization, additional carriers, multi-step processing, or prolonged development. In this study, we evaluated Facilitated Self-Assembling Technology (FAST) as a rapid carrier-free aqueous nanoformulation platform for eleven poorly water-soluble small-molecule drugs and one inorganic dental material. Ten selected compounds were representative BCS Class II drugs: celecoxib, itraconazole, rifampin, sorafenib, spironolactone, carvedilol, ezetimibe, lurasidone, rivaroxaban, and fenofibrate. Propofol was included as an additional clinically important hydrophobic drug to introduce the concept that FAST may enable “me-better” formulation opportunities for approved drugs with route-specific delivery limitations. Omyadent HA100 hydroxyapatite was included as a proof-of-concept inorganic oral-care material because hydroxyapatite is widely used as a biomimetic dental mineral and nanoscale hydroxyapatite has been investigated for enamel/dentin remineralization and dentin tubule occlusion; the HA100 experiment was designed to evaluate whether FAST could generate nanoscale mineral clusters under mild aqueous conditions. Using FAST, the selected drugs were converted into aqueous nanoscale dispersions and characterized by dynamic light scattering (DLS)/ZetaView analysis. In the initial ten-drug dataset, all formulations were generated and characterized within a same-day workflow, with particle sizes primarily in the nanoscale range and negative zeta potentials. Propofol, itraconazole, and rifampin were evaluated using the same analytical scheme, including particle size, particle concentration, zeta potential, visual dispersion stability, and TEM imaging. Omyadent HA100 was evaluated by DLS/ZetaView and TEM as an inorganic proof-of-concept material. TEM imaging of itraconazole revealed mixed morphology, including rod- or needle-like crystalline/nanocrystalline structures and rounded nanoscale particles, while rifampin showed heterogeneous rounded/oval particles and irregular nanoscale clusters in a clear brown/amber suspension. Together, these studies test whether FAST can rapidly generate carrier-free aqueous nanoformulations across chemically diverse poorly soluble drugs and a nanoscale hydroxyapatite material. The current study does not claim improved dissolution, pharmacokinetics, bioavailability, or therapeutic efficacy for each drug. Instead, it establishes a formulation-feasibility framework. If further studies confirm improved dissolution, stability, drug loading, route-specific delivery, pharmacokinetics, and safety, FAST may provide a rapid self-assembly platform for early formulation screening, drug repurposing, AI-assisted drug discovery, and me-better development of approved drugs with formulation-limited clinical performance.

Poor aqueous solubility remains a major challenge in formulating BCS Class II and IV drugs, while therapeutic peptides face additional challenges in stability and biological delivery. In the present study, we evaluated Facilitated Self-Assembling Technology (FAST) for the rapid preparation of aqueous nanosuspensions of 11 clinically relevant small-molecule drugs and two lipidated peptides, semaglutide and retatrutide. The compounds represent diverse structural classes and therapeutic uses, including targeted anticancer agents, immunosuppressants, anti-inflammatory drugs, and incretin-based peptides. Nanoparticle tracking analysis detected FAST-generated nanoscale particle populations in all 13 preparations, with number-weighted mean diameters from 126.7 to 219.1 nm and particle concentrations from 9.0 × 10⁷ to 5.4 × 10⁹ particles/mL. Semaglutide and retatrutide yielded mean diameters of 126.7 ± 55.6 and 163.0 ± 64.6 nm, respectively. All preparations exhibited negative zeta potentials. Paired-vial photographs showed similar aqueous appearances after more than 30 days at room temperature, except a slightly darker color in the venetoclax preparation. Transmission electron microscopy demonstrated predominantly rounded nanoscale particles in representative adagrasib and cyclosporine preparations. X-ray diffraction profiles of six selected FAST-generated BCS Class II/IV drug formulations exhibited broad, diffuse features near 20° 2θ, suggesting low apparent crystalline order and amorphous-like characteristics, which may favor improved dissolution of poorly water-soluble drugs. Taken together, these results support our hypothesis that FAST can generate aqueous nanoparticle preparations from clinically important compounds with widely different molecular structures. The extension to lipidated peptides suggest opportunities for future development of alternative peptide formulations and delivery systems.