Poly‐γ‐Glutamic Acid Microgel‐Encapsulated Probiotics with Gastric Acid Resistance and Smart Inflammatory Factor Targeted Delivery Performance to Ameliorate Colitis

Abstract

Hydrogel microspheres with probiotic-loaded therapy have been considered an effective and safe strategy for treating inflammatory bowel disease (IBD). However, the low survival rate under harsh stomach conditions and inflammatory cytokine target release efficiency remains a major challenge for their application. Herein, a novel NO-responsive poly-γ-glutamic acid (γ-PGA) hydrogel microcapsule (NRPM) strategy based on a droplet microfluidic technology platform is proposed. Accordingly, highly uniform microspheres with high cell densities (6.0 × 10 8 cells mL −1 ) and a wide range of diameters (100-600 μm) are produced, which are critical for realizing accurate downstream evaluation and applications. Owing to the cytoprotective effects of the NRPM, the decorated probiotics showed high viability in the simulated gastric (89.67%) and intestinal (93.67%) fluid environments, while the data are 0% and 61.60% for free cells, respectively. Moreover, both in vitro and in vivo studies demonstrate that microspheres can respond to nitric oxide (NO) stimuli and rapidly release probiotics to maintain the intestinal mechanical barrier and regulate the balance of intestinal flora. Consequently, NRPM significantly increases the treatment efficacy against dextran sulfate sodiuminduced colitis in a mouse model. The results demonstrate that NRPM is a promising approach for improving the efficacy of orally administered probiotics in patients with colonic IBD.

Living Probiotics-Loaded Hydrogel Microspheres with Gastric Acid Resistance and ROS Triggered Release for Potential Therapy of Inflammatory Bowel Disease

“…Following oral administration, maintaining high survival rate and activity of probiotics under the harsh stomach conditions and bile salts in the small intestine was a huge challenge. , As depicted in Figure b, own to the strong acid resistance of the Gel-Pa-HMs, the encapsulated L. plantarum could be fully protected from GI damage. Thus, the Gel-Pa-HMs@LP could be precisely delivered to the intestinal inflammatory area (with a relatively high H 2 O 2 concentration of 0.1 mM), so that the highly active probiotics were rapidly released from the microspheres triggered by the ROS, and proliferate fast to realize regulate flora balance and treatment.…”

Hydrogels as promising carriers for the delivery of food bioactive ingredients

“…In terms of drug delivery, hydrogel-loaded probiotics have a more specific orientation. The novel γ-glutamate hydrogel microcapsule will rapidly release probiotics when response to nitric oxide stimulation to maintain the integrity of the intestinal barrier and regulate the balance of gut microbiota, thus improving the therapeutic effect of sodium glucan sulfate induced colitis ( 130 ). In this study, the generation of NO caused by intestinal inflammation was utilized as a stimuli to trigger the breakup of the γ-glutamate hydrogel microcapsule, to release the encapsulated probiotics.…”

Oral polyphenol-armored nanomedicine for targeted modulation of gut microbiota–brain interactions in colitis

“…Inflammatory bowel disease (IBD), primarily Crohn’s disease and ulcerative colon inflammation, is an idiopathic disease with relapsing, refractory, and uncontrolled inflammatory responses in the ileum, rectum, and colon ( 1 , 2 ). Accumulating evidence supports oxidative stress and gut microbial disturbances as crucial triggers for IBD ( 3 , 4 ).…”