Colon-targeted pH-responsive tofacitinib beads improve ulcerative colitis outcomes with lower systemic exposure

Area of Science:

• Pharmacology
• Gastroenterology
• Biomaterials Science

Background:

• Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by mucosal inflammation and ulceration.
• Systemic administration of tofacitinib, a Janus kinase inhibitor, is effective for UC but associated with adverse effects.
• Targeted drug delivery aims to improve efficacy and reduce side effects.

Purpose of the Study:

• To design and evaluate a colon-targeted tofacitinib delivery system using sodium alginate beads coated with Eudragit® S-100.
• To assess the therapeutic efficacy and safety profile of this targeted delivery system in a dextran sulfate sodium (DSS)-induced colitis rat model.

Main Methods:

• Tofacitinib was encapsulated in sodium alginate beads and coated with Eudragit® S-100 for pH-dependent release.
• In vitro characterization included size, encapsulation efficiency, stability, and drug release studies.
• In vivo evaluation involved a 30-day DSS colitis model assessing histopathology, cytokine profiles, and drug concentrations.

Main Results:

• The colon-targeted beads demonstrated pH-dependent release, with minimal release in acidic conditions and maximum release at colonic pH.
• The formulation significantly improved disease activity scores and preserved colonic architecture in the DSS model.
• Pro-inflammatory cytokines were reduced, IL-10 levels increased, and colonic drug levels were higher with reduced systemic exposure compared to non-formulated tofacitinib.

Conclusions:

• The colon-targeted tofacitinib delivery system effectively delivered the drug to the colon, improving therapeutic efficacy in experimental colitis.
• This targeted approach potentially limits systemic exposure compared to conventional oral administration.
• Further toxicological and long-term safety studies are necessary to confirm the safety of this formulation.