Development and Characterization of a New Endoscopic Drug-Eluting Platform With Proven Efficacy in Acute and Chronic Experimental Colitis

Frontiers in Medicine

article

Ignacio Bon¹  Mary Cano-Sarabia²  Napoleon de la Ossa³  Ramon Bartolí¹  Vicente Lorenzo-Zúñiga¹ 

[1] Health Research Institute Germans Trias i Pujol (IGTP);Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and The Barcelona Institute of Science and Technology, Campus de la UAB;Hospital Universitari General de Catalunya—Grupo Quirón Salud;Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD);Endoscopy Unit, University Hospital La Fe

关键词: drug-eluting;    experimental colitis;    endoscopic shielding technique;    hydrogel;    endoscopy;   

DOI  :  10.3389/fmed.2020.00415

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Background and Aims: Mucosal lesions refractory to biological treatments represent unmet needs in patients with inflammatory bowel disease (IBD) that require new treatment modalities. We developed and characterized a new endoscopic drug-eluting hydrogel (CoverGel) with proven efficacy in acute and chronic experimental colitis (EC) in rats. Methods: CoverGel was developed based on appropriate rheological, drug release, gelation, structural, and degradation property capacities to allow endoscopic application. Experimental colitis (EC) was induced by TNBS application in rats. In acute EC 40, rats were randomized in five groups (eight each): Sham, Control, CoverGel, CoverGel + Infliximab (IFX) and CoverGel + Vedolizumab (VDZ). In chronic EC, 12 rats were randomized in two groups (six each): IFX s.c. and CoverGel + IFX. Endoscopic, histological, and blood test were performed during follow-up to evaluate clinical success. Antibodies to IFX (ATIs) were evaluated in chronic EC animal study. Results: CoverGel is a biocompatible and bioadhesive reverse thermosensitive gelation hydrogel with a macroporous structure and drug release capacity. In acute EC animals treated with CoverGel + IFX or CoverGel + VDZ showed significantly clinical success (weight recovery, mucosal restoration, and bacterial translocation) as compared with controls and animals without a bioactive drug. In a chronic EC animal study, clinical efficacy was comparable in both groups. Levels of ATIs were significantly lower in animals treated with CoverGel + IFX vs. IFX s.c. (0.90 ± 0.06 μg/mL-c vs. 1.97 ± 0.66 μg/mL-c, p = 0.0025). Conclusions: CoverGel is an endoscopic vehicle to locally deliver biological drugs with proven efficacy in acute and chronic EC in rats and induce less immunogenicity reaction.

【 授权许可】

CC BY