Mesalamine in Treatment of Intestinal Inflammatory Diseases-Formulation-Driven Strategies for Targeted Colonic Therapy and Remission Maintenance.

Mesalamine (5‑aminosalicylic acid, mesalazine, or 5‑ASA) remains a cornerstone therapy for mild‑to‑moderate ulcerative colitis because of its local anti‑inflammatory and antioxidant actions on the intestinal mucosa, and its clinical performance has increasingly been refined through advances in synthetic medicinal chemistry and drug‑delivery science. Beyond conventional formulations, medicinal chemistry efforts have explored mesalamine analogues and hybrid molecules, including prodrug approaches and conjugates with anti‑inflammatory or redox‑modulating moieties, to extend target engagement beyond classical cyclooxygenase inhibition toward pathways such as oxidative stress regulation and inflammasome signaling, thereby offering the potential for synergistic, multi‑pathway control of mucosal inflammation. In parallel, nanoparticle‑based delivery systems-such as pH‑responsive polymeric nanoparticles, mucoadhesive nanocarriers, and multi‑matrix or hydrogel‑based platforms-have been developed to protect mesalamine from premature upper gastrointestinal absorption, exploit disease‑associated pH and permeability changes, and prolong residence time at inflamed colonic sites, resulting in higher local drug concentrations with reduced systemic exposure. These strategies complement established oral and topical formulations and combination regimens, with preclinical and early translational data suggesting improvements in mucosal healing, attenuation of oxidative injury, and enhanced adherence through simplified dosing. When viewed together with emerging combination strategies that pair mesalamine with agents such as budesonide, sucralfate, or antioxidant and immunomodulatory compounds, these advances underscore a broader shift toward precision‑designed mesalamine therapies, integrating molecular optimization and targeted delivery to improve clinical outcomes in ulcerative colitis and to support exploratory roles in related inflammatory enteropathies.