A novel sodium caseinate lipid-based auto-emulsifying delivery system to increase resveratrol intestinal permeation: Characterization and in vitro assessment

Abstract

In recent years, nutraceuticals have emerged as a promising strategy for maintaining health and represent a high-growth market in Italy and across Europe. However, the lack of strict regulations regarding formulation requirements and proof of efficacy raises serious concerns about their poor bioavailability and, consequently, their uncertain health benefits. An emblematic example is t-resveratrol (RES), a cardioprotective stilbene polyphenol that undergoes extensive metabolism in the intestine and liver, resulting in a bioavailability of <1 %.

This manuscript describes a novel technological matrix developed with the primary goal of improving RES oral bioavailability. This technology can be classified as a lipid-based autoemulsifying drug delivery system (LIBADDS), in which RES is thoroughly solubilized in a hot liquid phase composed of lipids and surfactants, and the mixture is further adsorbed onto a powder composed of polysaccharides and sodium caseinate (N_aC), along with inert excipients, and then compressed.

In this study, NaC was used for the first time to trigger pancreatin-mediated hydrolysis of an enteric-coated tablet, allowing micellar delivery of RES to the small intestine. The RES-containing tablets were characterized via differential scanning calorimetry (DSC) and X-ray diffraction (PXRD). The digested formulation, with simulated gastric and enteric fluids, was dimensionally assessed via dynamic light scattering (DLS). Finally, calculations of the bioaccessible fraction, dissolution tests, and in vitro permeability experiments using Caco-2 cell monolayers were carried out to preliminarily define the overall efficiency and applicability of this new technology in improving RES intestinal permeability.