Abstract:
In Ulcerative Colitis (UC), the therapeutic efficacy of Nanoparticle (NP)-based drug delivery systems is limited by premature drug release, uptake or degradation of NPs during their passage through the harsh Gastrointestinal Tract (GIT) environment, poor colon targeting, and rapid NP clearance caused by diarrhea symptoms. This study focused on designing an advanced spatiotemporally controlled nanohybrid hydrogel drug delivery system to overcome these challenges. We developed a pH- and temperature-responsive polysaccharide-based hydrogel composed of Chitosan (CS), β-Glycerol Phosphate disodium salt pentahydrate (GP), Hydroxypropyl Cellulose (HPC), and collagen type I (Col I). The prepared Curcumin Nanoparticles (CurNPs) were encapsulated within the hydrogel to form the CS/HHPC/Col I-GP-CurNPs composite. The polysaccharide-based hydrogel shell of the formulation withstood harsh gastrointestinal conditions, enabled targeted adhesion to the colon, and was specifically degraded by colonic enzymes. The CurNPs released in the colon benefit from their negatively charged characteristics, enabling accumulation at the positively charged inflamed sites and achieving sustained Cur release. In vivo and in vitro data confirmed that the formulation significantly alleviated colitis symptoms by modulating the repolarization of pro-inflammatory M1 macrophages to anti-inflammatory M2 phenotypes and deactivating the TLR4/MyD88/NF-κB pathway. Furthermore, the integrity of the intestinal mucosal barrier and the gut microbiota were enhanced.
