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

Abstract

Brief summary: Direct drug administration through endoscopy opens new possibilities for therapeutic endoscopy in IBD. CoverGel is an endoscopic vehicle to locally deliver biological drugs with proven efficacy in acute and chronic experimental colitis in rats and inducing less immunogenicity reaction. ABSTRACTBackground&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 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) andCoverGel+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 Results: CoverGel 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). Conclusions:CoverGel is an endoscopic vehicle to locally deliver biological drugs with proven efficacy in acute and chronic EC in rats and inducing less immunogenicity reaction.Nowadays we do not have any valid endoscopic treatment to IBD mucosal lesions in patients with refractory or loss of response to biological therapy. The purpose of the present study was to develop and characterize a new endoscopic drug-eluting platform and test its efficacy in acute and chronic experimental colitis in rats. METHODS Characterization of the drug-eluting platformWe have developed a new hydrogel (CoverGel) comprising specific amounts of hyaluronic acid (HA), methylcellulose (MC) and Poloxamer Pluronic-F127 (F127). This platform has been patented (PCT/EP2017/068876). The composition of CoverGel is based on the combination of different substances to create this solution, which can be prepared before the procedure.Our goal was to improve the beneficial effects of HA onto the colonic mucosa by adding different substances to increase biocompatibility, bioadhesibility and bioactive properties, and make it suitable to be administered through the endoscope's working channel. For this, we e...

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

“…We would also like to thank the Endoscopy Unit and the Digestive Service at the University Hospital Germans Trias I Pujol. This manuscript has been released as a pre-print at Biorxiv, Bon et al (26).…”