A nanoparticle platform for combined mucosal healing and immunomodulation in inflammatory bowel disease treatment

• Published in: Bioactive materials 2024-02, Vol.32, p.206-221
• Main Authors: Marotti, Valentina, Xu, Yining, Bohns Michalowski, Cécilia, Zhang, Wunan, Domingues, Inês, Ameraoui, Hafsa, Moreels, Tom G., Baatsen, Pieter, Van Hul, Matthias, Muccioli, Giulio G., Cani, Patrice D., Alhouayek, Mireille, Malfanti, Alessio, Beloqui, Ana
• Format: Article
• Language: English
• Subjects: GLP-2; IBD; Inflammatory bowel disease; KPV; Nanocarrier; Teduglutide
• ISSN: 2452-199X; 2452-199X
• DOI: 10.1016/j.bioactmat.2023.09.014

Current treatments for inflammatory bowel disease (IBD) treatment consist of anti-inflammatory products. In this study, we sought to induce the physiological secretion of glucagon-like peptide 2, a peptide with intestinal growth-promoting activity, via nanoparticles while simultaneously providing with immunomodulation by tailoring the nanoparticle surface. To this end, we developed hybrid lipid hyaluronate-KPV conjugated nanoparticles loaded with teduglutide for combination therapy in IBD. The nanocarriers induced (or did not induce) immunosuppression depending on the presence (or absence) of a hyaluronan-KPV functionalization. This strategy holds promise as a nanoparticle platform for combined mucosal healing and immunomodulation in IBD treatment. [Display omitted] •As proof-of -concept, we have demonstrated that lipid nanocapsules per se increased GLP-2 secretion in vitro and in vivo in a murine acute colitis model (DSS) while increasing citrulline (mucosal healing marker) and decreasing the colon weight/length ratio (hallmark of this model).•We encapsulated teduglutide within lipid nanocapsules and tested in vivo in two acute models of colitis (DSS and TNBS) the mucosal healing and anti-inflammatory properties of the formulation, demonstrating no immunomodulatory effect of the nanocarriers per se with increased GLP-2 levels.•We synthesized hyaluronan-KPV conjugates and functionalized our teduglutide-loaded nanocarriers demonstrating combined anti-inflammatory and mucosal healing properties in an acute DSS model and in a chronic DSS model (50 days) upon intermittent administration.•The pharmacological effect exerted by our nanocarriers induced sufficient stimulus as per providing with mucosal healing upon intermittent administration of our formulation during 3 consecutive days, 3 times over 50 days, 9 doses in total.