Zein/HP-β-CD Nanoparticles for Theaflavins Encapsulation: Enhanced Stability, Sustained Release, and Protective...

Theaflavins (TFs), the major bioactive polyphenols in black tea, possess potent antioxidant and anti-tyrosinase activities, but their practical application is severely limited by poor chemical stability and low bioavailability. To overcome these drawbacks, we engineered zein/cyclodextrin composite nanoparticles to enhance the stability and bioactivity of TFs. Among three cyclodextrins including β-cyclodextrin (β-CD), γ-cyclodextrin (γ-CD), and hydroxypropyl-β-cyclodextrin (HP-β-CD), the Zein/HP-β-CD formulation was optimal, yielding a particle size of 137 nm, a polydispersity index as low as 0.06, an encapsulation efficiency of 96.7%, and robust colloidal stability under various pH, temperature, and ionic strength conditions. Structural analyses confirmed the formation of spherical amorphous nanocomposites stabilized by hydrogen bonding and hydrophobic interactions. Compared with free TFs, Zein/HP-β-CD@TFs nanoparticles exhibited superior antioxidant activity with a DPPH radical scavenging rate of 79.5% and a 3-fold lower IC50 for tyrosinase inhibition. In ultraviolet (UV) B-irradiated HaCaT cells, the nanoencapsulated TFs increased cell viability from 64.1% to 87.7%. In a zebrafish whitening model, the nanoparticles achieved 35.0% melanin inhibition at a total mass concentration of 0.025%, which was 1.4-fold higher than that of free TFs at the same concentration, while also exhibiting a 4-fold higher safety margin with a maximum tolerated concentration of 0.1% compared with 0.025% for free TFs. These findings demonstrate that Zein/HP-β-CD nanoparticles serve as an effective delivery platform by establishing a structure-activity relationship linking molecular interactions to enhanced bioactivity, improving the stability, bioavailability, and health-promoting functions of TFs for cosmetic and nutraceutical applications.