Enteric-coated gelatin nanoparticles mediated oral delivery of 5-aminosalicylic acid alleviates severity of DSS-induced ulcerative colitis

Ulcerative colitis (UC) is an inflammatory condition involving ulcers in colon and rectum. Conventional treatments for colitis confront serious limitations like off target systemic side effects, drug degradation and inactivation, restricted absorption and other complications culminating in poor bioavailability. These limitations necessitate localized drug delivery to inflamed colon such that drug can bypass abrasive gastric surroundings, availing protection form gastric acid and has selective access to colonic mucosa. Therefore, present study was designed to formulate Eudragit-S100 coated 5-amino salicylic acid (5-ASA)-loaded gelatin nanoparticles (NPs) for localized delivery of 5-ASA for treatment of ulcerative colitis. NPs were formulated by nanoprecipitation and solvent evaporation method, had hydrodynamic diameter of 225-250 nm, smooth and spherical surface morphology under TEM, SEM and AFM. Oral administration of NPs ameliorated disease activity indices like fecal occult bleeding, colon length and stool consistency. NPs treatment significantly reduced mast cells infiltration in colon, restored protective mucin layer and appreciably reinstated colonic histoarchitecture. Furthermore, inflammatory biomarkers like TNF-alpha, IL1-beta, COX-2, iNOS, myeloperoxidase and nitrite levels were also significantly reduced by NPs treatment. Overall, results of this study indicate that 5-ASA NPs possessed superior therapeutic efficacy over free 5-ASA in experimental colitis and these results are attributed to their ability to significantly suppress inflammation.

Automated summary

The study formulated Eudragit-S100 coated 5-ASA-loaded gelatin nanoparticles for localized delivery in ulcerative colitis treatment. The nanoparticles showed superior therapeutic efficacy over free 5-ASA by reducing disease activity, restoring colonic mucosa, and decreasing inflammatory biomarkers levels.