Among oral delivery systems, oil in water nano-emulsions (O/W NEs) are of particular interest to improve pharmacokinetics of lipophilic compounds. Recently, we have implemented a successful strategy to improve O/ W NEs stability, based on a polymeric coating on an oil core, namely secondary O/W NEs, through the use of pharma grade formulations. However, in the field of food supplements, food grade materials are the top choice since they combine safety and cost effectiveness. Here, we have replaced pharma grade (PG) with food grade (FG) materials in the preparation of the polymer coated O/W NEs, and performed a comparative study between the two formulations to assess the FG one. At the same time, in order to provide formulations with enhanced mucus-adhesion to the intestinal barrier, secondary O/W NEs were prepared by adding thiol groups to chitosan (Ct) via a simple non-covalent procedure based on N-acetyl-cysteine (NAC) salification, thus easily implementable to a food supplement formulation. PG and FG formulations, in different materials combinations, were prepared and physico-chemically characterized (DLS, 1H NMR, ITC, CRYO-TEM) showing similar behaviour. FG formulations (NEs, Ct-NEs and Ct-NAC-NEs) loaded with curcumin were prepared and compared with the free drug in terms of drug bioaccessibility through the INFOGEST protocol confirming improved bioaccessibility. Very interestingly, by comparing mucus-adhesion properties of the two polymeric coatings (Ct and Ct-NAC) within an intestine on chip device able to mimic the complex intestinal functions, a significant enhancement in the mucus-adhesive properties of the proposed novel Ct-NAC-NE formulation was observed with respect to Ct due to the presence of thiol groups. Nonetheless, in-vivo assays are required as a final assessment of the proposed system.
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