Electrostatically sprayed alginate-carboxymethyl chitosan microgel for colon-targeted melatonin delivery ameliorates ulcerative colitis

The present study fabricated melatonin-loaded sodium alginate/carboxymethyl chitosan (Mel/SA-CMC) microgel as a colon-targeted therapeutic strategy for ulcerative colitis. Optimization of the SA/CMC ratio (1:1) and voltage (15 kV) produced Mel/SA-CMC microgels with maximum encapsulation efficiency (91.8 % f 1.2 %) and loading capacity (16.4 % f 0.1 %). Characterization techniques, including scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and thermogravimetric analyses, elucidated the physicochemical properties of the microgels. Simulated digestion experiments and pharmacokinetic analyses indicate that the microgels remain stable in the gastric environment (pH = 3.5) and release melatonin in a controlled manner in the colonic environment (Tmax = 4 and AUC = 16,208 pg h/mL). In a dextran sodium sulfate (DSS)induced Caco-2 cell inflammation model, Mel/SA-CMC enhanced cell viability and attenuated oxidative stress and inflammatory response. Furthermore, administration of Mel/SA-CMC to mice with DSS-induced acute colitis alleviated the deleterious effects of DSS, as evidenced by preserved colon length (9.2 f 0.9 cm), mitigated histological damage (histological injury score: 1.5 f 0.5), and reduced expression of inflammatory cytokines (IL4, IL-6, IL-1 beta and TNF-alpha). Notably, Mel/SA-CMC restored gut microbiota composition by enriching beneficial genera, including Bifidobacterium, Ruminococcus2, and Lactobacillus, leading to elevated concentrations of shortchain fatty acids. In conclusion, the Mel/SA-CMC microgel demonstrates potent antioxidant and antiinflammatory properties as a potential therapeutic intervention for inflammatory bowel disease.