Bioactive chitosan-BSA Maillard-derived chrysin-loaded nanoparticles: A gastroprotective, biomucoadhesive approach for enhanced oral therapy in ulcerative colitis.

The current limitations of oral nanomedicines such as aminosalicylates, immunosuppressants, corticosteroids, and antibiotics include the toxic byproducts from nanocarrier synthesis, poor targeting and retention within the inflamed colon, delayed release at inflammation sites, susceptibility to gastric degradation, reduced efficacy under hypoxic conditions, MUC2 homeostasis disruption, and insufficiently addressing the disease's root causes. This research presents an innovative approach of using non-toxic, biodegradable, and biocompatible Maillard reaction-based nanoparticles (MPs) for targeted oral drug delivery in IBD therapy. Through the development of mucoadhevise chitosan-bovine serum albumin Maillard nanoparticles shielded with biocompatible, non-toxic, non-immunogenic, gastroprotective pectin (P@CMPs) encapsulating with chrysin, a flavonoid with anti-inflammatory and hyperoxia properties whose bioavailability is negatively affected by gastric degradation. P@CMPs had a spherical, uniform 300 nm hydrodynamic diameter, confirmed by TEM and FESEM. Chrysin encapsulation efficiency and loading capacity were ∼96 % and 16 %, respectively, demonstrating effective nanoparticle formulation The P@CMPs is designed to withstand the gastrointestinal environment, ensuring targeted delivery and prolonged retention in inflamed colonic regions. In a dextran sodium sulfate-induced colitis mouse model, P@CMPs markedly mitigated inflammation, suppressed proinflammatory cytokine levels, and augmented the expression of MUC2, a crucial factor for maintaining the integrity of the gut barrier. By employing non-toxic, biocompatible and biodegradable materials, our P@CMPs approach offers a promising avenue for advancing IBD treatment, addressing various challenges and precise oral delivery within the gastrointestinal system.