Abstract

Inflammatory bowel diseases (IBD) induce serious symptoms, but the current treatment approaches suffer from low bioavailability, poor patient compliance, and limited efficacy. Therefore, the development of advanced drug delivery systems for oral drugs is urgently needed. In this study, a hypoxia-responsive drug delivery platform was designed using Co2+ and olsalazine (OL) as the building blocks, followed by coating with dopamine-modified hyaluronic acid (HA-DA), yielding CoOL-HA-DA. The HA-DA coating achieves gastric acid protection and an extended intestinal residence time for 48 h with a colon-specific adhesion ability. The negative charge of CoOL-HA-DA enables targeted delivery to inflammatory sites and significant biological safety through the repulsion with the negative charge of the mucus layer. Yet, at diseased sites featuring reactive oxygen species (ROS), CoOL can eliminate ROS and release 5-aminosalicylic acid (5-ASA) to treat IBD under conditions of intestinal hypoxia. Both in vitro and in vivo results show that the CoOL-HA-DA improved the sustained release of 5-ASA, demonstrating its potent efficacy in IBD treatment with reduced side effects. Collectively, CoOL-HA-DA, as a hypoxia-responsive drug delivery platform, provides another medical approach for IBD and other gut disease management.