Oral hydrogel nanoemulsion co-delivery system treats inflammatory bowel disease via anti-inflammatory and promoting intestinal mucosa repair

Abstract

Background Due to oral nano-delivery systems for the treatment of inflammatory bowel disease (IBD) are often failed to accumulated to the colonic site and could not achieve controlled drug release, it’s urgent to develop a microenvironment responsive drug delivery to improve therapy efficacy. Inflammation at the IBD site is mainly mediated by macrophages, which are the key effector cells. Excessive inflammation leads to oxidative stress and intestinal mucosal damage. The use of curcumin (CUR) and emodin (EMO) together for the treatment of IBD is promising due to their respective anti-inflammatory and intestinal mucosal repair effects. In view of the pH gradient environment of gastrointestinal tract, here we prepared pH-responsive sodium alginate (SA) hydrogel-coated nanoemulsions to co-deliver CUR and EMO (CUR/EMO NE@SA) to achieve controlled drug release and specifically target macrophages of the colon. Results In this study, a pH-responsive CUR/EMO NE@SA was successfully developed, in which the CUR/EMO NE was loaded by chitosan and further crosslinked with sodium alginate. CUR/EMO NE@SA had a pH-responsive property and could achieve controlled drug release in the colon. The preparation could significantly alleviate and improve the colon inflammatory microenvironment by decreasing TNF-α and IL-6 expression, increasing IL-10 expression, scavenging reactive oxygen species in macrophages, and by ameliorating the restoration of intestinal mucosal tight junction protein expression. Furthermore, we revealed the molecular mechanism of the preparation for IBD treatment, which might due to the CUR and EMO synergic inhibition of NF-κB to improve the pro-inflammatory microenvironment. Our study provides a new IBD therapy strategy via synergically inhibiting inflammatory, repairing mucosal and clearing ROS by pH-sensitive hydrogel-encapsulated nanoemulsion drug delivery system, which might be developed for other chronic inflammatory disease treatment. Conclusions It’s suggested that pH-sensitive hydrogel-coated nanoemulsion-based codelivery systems are a promising combinatorial platform in IBD. Graphical Abstract

Polyphenolic Nanoparticle-Modified Probiotics for Microenvironment Remodeling and Targeted Therapy of Inflammatory Bowel Disease

“…The overabundance of ROS and the proinflammatory microenvironment could damage intestinal tissue and induce the destruction of crucial gut proteins and ultimately impair the integrity of the intestinal barrier. As the main junctions between epithelial cells of the intestinal mucosa, tight junctions are vital for the maintenance of intestinal homeostasis . We then investigated the epithelial barrier integrity by assessing the colonic expression levels of tight junctions ZO-1 and Occludin.…”

“…As the main junctions between epithelial cells of the intestinal mucosa, tight junctions are vital for the maintenance of intestinal homeostasis. 37 We then investigated the epithelial barrier integrity by assessing the colonic expression levels of tight junctions ZO-1 and Occludin. As shown in Figure 7A−D, immunohistochemistry images revealed significantly reduced fluorescence in the DSS model group, indicating that the expression levels of ZO-1 and Occludin in the colon were significantly downregulated.…”

Biomedical Trends in Stimuli-Responsive Hydrogels with Emphasis on Chitosan-Based Formulations

“…Three-dimensional molecular networks can also be administered to the patient through injections, which allow for precise delivery of the substance to the targeted area, such as the knee joint [43]. Another route is oral administration since hydrogels can effectively cope with the low pH of the stomach or even release the active substance in response to the acidic environment [44]. Biomaterials can also be delivered via ocular, nasal, vaginal, and rectal administration [45][46][47][48].…”

Advancing Gastrointestinal Health: Curcumin’s Efficacy and Nanopreparations

“…Lei et al [75] prepared a Ph-responsive sodium alginate (SA) hydrogel-coated nanoemulsion that co-delivers CCM and emodin (EMO) CUR/EMO NE@SA, controls drug release in the colon, and specifically targets colonic macrophages. In preclinical studies, CUR/EMO NE@SA was shown to improve the inflammatory microenvironment of the colon by modulating inflammatory signaling and scavenging ROS from macrophages.…”