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

Abstract

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.

Endoscopic Management of Strictures in Crohn’s Disease: An Unsolved Case

“…The dual potential of NPs as drug-eluting and detectable nanovehicles represents an exciting perspective in IBD, potentially leading to dose-controlled and selective insite bioavailability of a drug or a therapeutic intervention targeting inflamed mucosa [83]. Among intestinal delivery systems, another remarkable product recently developed is a biocompatible hydrogel amenable to the endoscopic application (CoverGel), showing intriguing preclinical data; in experimental colitis mice, when comparing CoverGel + IFX versus subcutaneous IFX alone, it was observed similar efficacy on inflammation, with significantly lower levels of ATI in the CoverGel group [84].…”

Controlled Drug Release from Nanoengineered Polysaccharides

“…Based on these in vivo studies, it was reported that 3D BNC only induced a mild acute inflammatory response, not a foreign body or chronic inflammatory response, and did not affect the wound’s ability to heal [ 207 ]. Another study [ 208 ] developed a hydrogel based on hyaluronic acid (HA), methylcellulose (MC), and Poloxamer Pluronic-F127 (F127). It was developed as an endoscopic vehicle for delivering biological drugs with proven efficacy in acute and chronic EC in rats while causing less immunogenicity.…”