Ulcerative colitis (UC) with continuous and extensive inflammation is limited to the colon mucosa and can lead to abdominal pain, diarrhea, and rectal bleeding. Conventional therapies are associated with several limitations, such as systemic side effects, drug degradation, inactivation, and limited drug uptake, leading to poor bioavailability. These restrictions necessitate drug delivery to the colon so that the drug passes through the stomach unchanged and has selective access to the colon. The present study aimed to formulate 5-aminosalicylic acid (5-ASA) and berberine (BBR) in chitosan nanoparticles cross-linked by HPMCP (hydroxypropyl methylcellulose phthalate) as a colon drug delivery system for UC. Spherical nanoparticles were prepared. They showed appropriate drug release in the simulated intestinal fluid (SIF), while the release did not occur in the simulated gastric fluid (SGF). They improved disease activity parameters (DAI) and ulcer index, increased the length of the colon, and decreased the wet weight of the colon. Furthermore, histopathological colon studies showed an improved therapeutic effect of 5-ASA/HPMCP/CSNPs and BBR/HPMCP/CSNPs. In conclusion, although 5-ASA/HPMCP/CSNPs showed the best effect in the treatment of UC, BBR/HPMCP/CSNPs, and 5-ASA/BBR/HPMCP/CSNPs were also effective in vivo study, and this study anticipated they could be helpful in future clinical applications for the management of UC.
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