Clinical combination therapy for IBD and promising co-delivery strategies.

Biological agents are the cornerstone of first-line treatment for inflammatory bowel disease. However, approximately 33% of patients either fail to respond initially or experience diminished efficacy over time. The use of combination therapies, such as pairing biological agents with immunomodulators or small-molecule drugs, has proven effective in enhancing efficacy and mitigating resistance. For instance, the combination of infliximab and azathioprine elevated corticosteroid-free clinical remission and mucosal healing rates in patients with ulcerative colitis to 39.7 and 62.8%, respectively; triple therapy with vedolizumab, adalimumab, and methotrexate raised the week 10 clinical remission rate in patients with Crohn's disease to 61.8%; and combining guselkumab with golimumab increased the response rate in patients with ulcerative colitis to 83%. Despite these successes, challenges remain in optimizing dosing regimens and managing systemic toxicities. Nanocarriers offer a solution by encapsulating one or more drugs within a single system, facilitating targeted delivery, simplifying treatment protocols, and minimizing toxicity. Research indicates that advanced delivery systems, including poly(lactic-co-glycolic acid) nanoparticles, mulberry leaf liposomes, and sodium alginate hydrogels, can enhance anti-inflammatory effects, promote mucosal healing, and modulate the gut microbiota, providing effective colitis treatment. This review examines combination dosing strategies for inflammatory bowel disease, nanodelivery methods, and novel approaches to advance the clinical application of nanodelivery technology in combination therapies.