ROS-responsive microparticles with targeting for activated macrophages and colon-specific release of mesalazine as a potential strategy for treating inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) is an autoimmune disorder of unknown etiology characterized by chronic inflammation of the gastrointestinal tract (GIT). The first-line drug used in the treatment of mild to moderate IBD is the anti-inflammatory drug 5-aminosalicylic acid (5-ASA). As this drug is quickly absorbed in the first portions of the GIT and arrives in low concentrations in the colonic region, there is a need for high dosages for the treatment to be effective, which promotes several side effects. Therefore, it is important to develop other therapies to targeting the release of 5-ASA to the colonic region, such as colon-specific oral delivery systems (CSODDSs). Natural polysaccharides such as retrograded starch (RS) and pectin (P) are considered a promising strategy for the development of CSDDSs activated by the colonic microbiota, since these substances escape digestion in the upper portions of the GIT and are selectively degraded by secreted enzymes by the colon microbiota. RS can be obtained through the retrogradation process and, when associated with P, has a higher yield in its contents. Furthermore, the gastrointestinal mucosa of patients with IBD has a high concentration of activated macrophages, which overexpress class-A scavenger receptors (SR-A) on their surface, enabling the targeting of polymeric carriers to the inflamed region through the use of dextran sulfate (DS), a ligand of SR-A receptors. In addition, a promising strategy for eliminating the excessive presence of reactive oxygen species (ROS) in the inflamed area and developing ROS-responsive microparticles is using 1,4-phenylenediboronic acid (Pa), a chemical crosslinker which makes the drug reach the inflamed region effectively. This work provides universal and viable alternatives to precisely deliver the drug 5-ASA to intestinal inflammatory areas, promising to meet the needs of targeted therapy for IBD.