Development and characterization of mucoadhesive and ROS-responsive microparticles for colon-specific mesalazine delivery in the treatment of ulcerative colitis.

• Grant number: 25/14530-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2025
• End date: September 30, 2026
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Andréia Bagliotti Meneguin
• Grantee: Augusto Cardoso de Oliveira
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Inflammatory Bowel Disease (IBD), which includes Crohn's disease and ulcerative colitis (UC), is a chronic condition of the gastrointestinal tract (GIT) characterized by inflammation and an impaired quality of life. Although 5-aminosalicylic acid (5-ASA) is a first-line therapy for mild to moderate UC, its efficacy is limited by rapid absorption and metabolism in the upper GIT. This results in low drug concentrations in the colon, the primary site of the disease, necessitating high doses that increase the risk of adverse effects. These pharmacokinetic challenges highlight the need for more effective, colon-targeted drug delivery systems. Oral colon-specific delivery systems, particularly polysaccharide-based microparticles (MPs), represent a promising alternative to overcome these limitations, offering multifunctionality by responding to various pathophysiological stimuli. Among production techniques, spray drying is notable as a continuous, low-cost process that enables both microencapsulation and drying in a single step. In this context, the development of 5-ASA-loaded MPs using materials responsive to the colonic microenvironment has been explored. Natural polysaccharides like retrograded starch (RS), obtained through gelation and retrogradation, are a valuable strategy as they resist digestion in the upper GIT and are selectively degraded by enzymes from the colonic microbiota, providing passive targeting to the colon. To enhance selectivity and improve delivery to inflammatory sites in UC, the incorporation of hyaluronic acid (HA) is a promising approach. HA imparts mucoadhesive properties to the MPs, aiding their retention in the colon, which is crucial given the increased intestinal motility in IBD patients. Furthermore, to optimize drug release within the disease microenvironment, systems responsive to reactive oxygen species (ROS) have been developed. The chemical crosslinking of MPs with compounds such as 1,4-phenylenediboronic acid (PDBA) triggers the system's disassembly and the subsequent release of 5-ASA in response to elevated ROS concentrations in inflamed areas. In summary, the combination of passive targeting, active retention, and responsive release in MPs represents a promising strategy for the precise delivery of 5-ASA to inflamed intestinal regions, seeking to optimize IBD therapy.