Polyphenols-composed micelles: production, physicochemical characterization, <i>in silico</i> pharmacokinetics, and rheological behaviour of a new colloidal system for dual delivery of resveratrol and rutin

A new micellar delivery system for the dual loading of resveratrol and rutin (RES-RU-micelles) is described and characterized. Analyzes were carried out to determine the size parameters (mean particle size and polydispersity index) and surface electrical charge, 24 h after production and after 2 months of storage at two different temperatures (4 °C and 25 °C). <i>In silico</i> ADME predictions revealed striking differences in skin permeability between resveratrol (Log <i>K</i>p = -5.47 cm/s) and rutin (Log <i>K</i>p = -10.26 cm/s). Molecular analysis demonstrated that the contrasting physicochemical properties of RES (Log <i>P</i> = 2.57, TPSA = 60.69 Å) and RU (Log <i>P</i> = -2.11, TPSA = 269.43 Å) enable their spatial segregation within the micelles. RES is located predominantly in the hydrophobic core through hydrophobic interactions, while RU positions at the core-shell interface <i>via</i> hydrogen bonding with the hydrophilic components. The encapsulation efficiency achieved values above 98% for both bioactives in the dual loading. The viscoelastic profile showed that the G' was higher than the G″ in the applied frequency range, demonstrating that the developed micelles are more elastic than viscous. DSC analysis showed the absence of peaks, corroborating that no bioactive crystallization happened when loaded into the micelles. Transmission electron microscopy analysis confirmed the morphology and spherical shape of the produced micelles.