Fiche publication
Date publication
août 2025
Journal
Drug delivery and translational research
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BOIDOT Romain
,
Pr BEDUNEAU Arnaud
Tous les auteurs :
Stalder T, Moulari B, Cornu R, Chatelain J, Koenig N, Hassan A, Chretien C, Boidot R, Richard C, Pellequer Y, Jurin F, Pierre H, Martin H, Béduneau A
Lien Pubmed
Résumé
Inflammatory bowel diseases (IBD) affect millions of people worldwide. The use of anti-TNF-α for the treatment of moderate-to-severe IBD faces primary non-response, loss of response during treatment or intolerance issues. As an alternative, a strategy consisting of oral administration of TNF-α siRNA was evaluated in the present study for the local treatment of IBD. TNF-α siRNA entrapped in lipid nanoparticles (LNPs) was microencapsulated in gastroresistant alginate particles using an original process. The encapsulation yield of both siRNA and LNPs in microparticles (MPs) was at least 90%. Oral administration of MPs significantly reduced both clinical score and therapeutic index in a TNBS-induced colitis model in mice. Near complete removal of tissue damage, including edema, ulceration and necrosis, was observed in colon sections from treated mice. Reduced variation in gene sets involved in the global inflammatory response and the TNF-α/NF-κB signaling pathway was detected in the colon compared to untreated mice, demonstrating the anti-inflammatory activity of MPs. Finally, biodistribution studies showed the targeting of the inflamed colon by MPs and the colocalization of LNPs and MPs at the site of action. These MPs may represent a promising siRNA delivery platform for the oral treatment of IBD.
Référence
Drug Deliv Transl Res. 2025 08 6;:
