2. Academic Validation
  3. Glepaglutide-Loaded Foam for the Induction of Mucosal Healing in the Treatment of Inflammatory Bowel Disease

Glepaglutide-Loaded Foam for the Induction of Mucosal Healing in the Treatment of Inflammatory Bowel Disease

  • Adv Healthc Mater. 2025 Feb 5:e2403497. doi: 10.1002/adhm.202403497.
Wunan Zhang 1,  William Van den Bossche 1,  Hafsa Yagoubi 1,  Espoir K Kambale 1,  Khadija Wahni 2 3 4,  Tanya Saxena 1,  Léo Guilbaud 1,  Tom G Moreels 5 6,  Joris Messens 2 3 4,  Ana Beloqui 1 7
Affiliations

Affiliations

  • 1 UCLouvain, Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Brussels, 1200, Belgium.
  • 2 VIB-VUB Center for Structural Biology, Brussels, 1050, Belgium.
  • 3 Brussels Center for Redox Biology, Brussels, 1050, Belgium.
  • 4 Structural Biology Brussels, Vrije Universiteit Brussel, Brussels, 1050, Belgium.
  • 5 Institute of Experimental and Clinical Research, Laboratory of Hepato-Gastroenterology, UCLouvain, Université Catholique de Louvain, Brussels, 1200, Belgium.
  • 6 Cliniques universitaires Saint-Luc, Department of Gastroenterology & Hepatology, Brussels, 1200, Belgium.
  • 7 WEL Research Institute, Avenue Pasteur, 6, Wavre, 1300, Belgium.
PMID: 39905897 DOI: 10.1002/adhm.202403497
Abstract

Glucagon-like peptide 2 (GLP-2) stimulates intestinal growth, repairs mucosa, and enhances epithelial integrity but has a short half-life (7 min). Glepaglutide (GL), a GLP-2 analog with an extended half-life (50 h), is currently undergoing clinical trials for patients with short bowel syndrome. GL requires subcutaneous injection, which poses challenges for potential patient compliance. To address this challenge, GL was loaded into a rectal foam formulation using CO2 as a permeation enhancer to combine both the local and systemic effects of the GLP-2 analog. In a dextran sodium sulfate (DSS)-induced colitis model, the GL-loaded foam (GLF) significantly mitigated the severity of colitis. GLF facilitated mucosal healing, as evidenced by colonoscopy images, increased plasma markers of mucosal healing, and increased crypt depth. To evaluate GL absorption in the colon, fluorescein dextran 4K (FD 4K) was employed. The foam formulation improved macromolecule absorption in the colon, with fast recovery of enhanced permeation that dissipated after 4 h. This study highlights GLF as a promising formulation for GL administration, balancing systemic and local anti-inflammatory effects.

Keywords

colon delivery; foam; gas permeation enhancer; glepaglutide; inflammatory bowel disease.

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