Formulation design, optimization and <i>in vivo</i> evaluation of oral co-encapsulated resveratrol-humic acid colloidal polymeric nanocarriers

The study aims at formulation and optimization of resveratrol and humic acid co-encapsulated colloidal polymeric nanocarriers to improve stability, oral bioavailability, and antiradical activity of water-insoluble, resveratrol. The eudragit E100 polymeric material was used to fabricate resveratrol and humic acid co-encapsulated oral colloidal polymeric nanocarriers (<i>Res</i>-HA-co-CPNs) using emulsification-diffusion-evaporation method. Taguchi orthogonal array design was employed to check the effect of formulation factors on <i>in vitro</i> physicochemical characteristics. The optimized formulation was further evaluated for oral bioavailability as well as for antiradical potential. Optimized <i>Res</i>-HA-co-CPNs demonstrated spherical and smooth surface including mean particle size, 120.56 ± 18.8 nm; polydispersity index, 0.122; zeta potential, +38.25 mV; and entrapment efficiency, 82.37 ± 1.49%. Solid-state characterization confirmed the amorphous characteristic of optimized <i>Res</i>-HA-co-CPNs. <i>In vitro</i> release profile of <i>Res</i>-HA-co-CPNs showed sustained release behavior up to 48 h and CPNs were found to remain stable at the refrigerated condition for 6 months. <i>In vivo</i> pharmacokinetic studies revealed significant (<i>p</i> < 0.05) improvement of ∼62.76-fold in oral bioavailability. The radical-scavenging activity was found to be increased with time and after 72 h, it was analogous to pure <i>Res</i>. IC₅₀ values were reported to be decreased with time. Henceforth, developed <i>Res</i>-HA-co-CPNs was proven to be a proficient dosage form to increase stability, oral bioavailability, and antiradical activity of resveratrol.HighlightsResveratrol-humic acid co-encapsulated colloidal polymeric nanocarriers (<i>Res</i>-HA-co-CPNs) were fabricated by emulsification-diffusion-evaporation method and optimized by Taguchi orthogonal array design.The <i>Res</i>-HA-co-CPNs revealed favorable mean particle size and percent encapsulation efficiency with a spherical and smooth surface.The <i>Res</i>-HA-co-CPNs showed diffusion-controlled release of <i>Res</i> and were found to be stable at the refrigerated condition for 6 months.The optimized <i>Res</i>-HA-co-CPNs demonstrated significantly (<i>p</i> < 0.05) higher oral bioavailability with respect to pure <i>Res</i> and PM.The optimized <i>Res</i>-HA-co-CPNs demonstrated higher radical-scavenging activity with respect to time.