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bioRxiv · 10.1101/712224

DEVELOPMENT AND CHARACTERIZATION OF A NEW ENDOSCOPIC DRUG ELUTING PLATFORM WITH PROVEN EFFICACY IN ACUTE AND CHRONIC EXPERIMENTAL COLITIS

Bon, I.·Cano-Sarabia, M.·De la Ossa, N.·Bartoli, R.·Lorenzo-Zuniga, V.
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Abstract

Background&AimsMucosal 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\n\nMethodsCoverGel was developed based on appropriate rheological, drug release, gelation, structural and degradation properties capacities to allow endoscopic application. Experimental colitis (EC) was induced by TNBS application in rats. In acute EC 40 rats were randomized in 5 groups (8 each): sham, control, CoverGel, CoverGel+Infliximab (IFX) and CoverGel+Vedolizumab (VDZ). In chronic EC 12 rats were randomized in 2 groups (6 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\n\nResultsCoverGel is a biocompatible and bioadhesive reverse thermo sensitive gelation hydrogel with 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 compare with controls and animals without bioactive drug. In 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 g/mL-c vs. 1.97 {+/-} 0.66 g/mL-c, p=0.0025).\n\nConclusionsCoverGel is an endoscopic vehicle to locally deliver biological drugs with proven efficacy in acute and chronic EC in rats and inducing less immunogenicity reaction.

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Bon, I., Cano-Sarabia, M., De la Ossa, N., Bartoli, R., Lorenzo-Zuniga, V.. 2019-07-23. DEVELOPMENT AND CHARACTERIZATION OF A NEW ENDOSCOPIC DRUG ELUTING PLATFORM WITH PROVEN EFFICACY IN ACUTE AND CHRONIC EXPERIMENTAL COLITIS. https://doi.org/10.1101/712224

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