Peptide-Based Hydrogel for Nanosystems Encapsulation: the Next Generation of Localized Delivery Systems for the Treatment of Intestinal Inflammations

Conventional therapies for inflammatory bowel diseases are mainly based on systemic treatments which cause side effects and toxicity over long-term administration. Nanoparticles appear as a valid alternative to allow a preferential accumulation in inflamed tissues following oral administration while reducing systemic drug exposure. To increase their residence time in the inflamed intestine, the nanoparticles are here associated with a hydrogel matrix. A bioadhesive peptide-based hydrogel is mixed with nanoemulsions, creating a hybrid lipid-polymer nanocomposite. Mucopenetrating nanoemulsions of 100 nm are embedded in a scaffold constituted of the self-assembling peptide hydrogel product PuraStat. The nanocomposite is fully characterized to study the impact of lipid particles in the hydrogel structure. Rheological measurements and circular dichroism analyses are performed to investigate the system's microstructure and physical properties. Biodistribution studies demonstrate that the nanocomposite acts as a depot in the stomach and facilitates the slow release of the nanoemulsions in the intestine. Efficacy studies upon oral administration of the drug-loaded system show the improvement of the disease score in a mouse model of intestinal inflammation. Local manipulation of immunological pathways causing intestinal inflammation represents a promising strategy for inflammatory bowel diseases treatment. Here, oral hybrid lipid-polymer nanocomposite made of bioadhesive peptide-based hydrogel mixed with tofacitinib-loaded nanoemulsions for local intestinal immunomodulation is designed. The feasibility of the nanocomposite platform and the efficacy upon oral administration in a mouse model of intestinal inflammation are demonstrated. image