CD‐MOF Based pH/ROS Sensitive 5‐ASA Delivery System for Ulcerative Colitis Therapy

Aminosalicylic acid (ASA)@CM is synthesized via hydrothermal and impregnation methods. Subsequently, ASA@CM is encapsulated within a sodium alginate-L-Arginine (SA-LA) complex using electrospray to obtain ASA@CM/SL microspheres. Following oral administration in mice, ASA@CM/SL treats ulcerative colitis (UC) by modulating inflammatory cytokine and reactive oxygen species (ROS) levels in the inflamed colon microenvironment, thereby restoring the intestinal barrier.

Abstract

5-Aminosalicylic acid (5-ASA) is the first-line drug for ulcerative colitis (UC), which encounters therapeutic constraints due to the poor water solubility and absorption by the upper gastrointestinal. Here, a cyclodextrin-based metal-organic framework (CD-MOF) is used as a carrier for 5-ASA (ASA@CM) to enhance its solubility. To improve the targeted release 5-ASA, ASA@CM is incorporated into sodium alginate/L-arginine complex (SA-LA) to obtain the desired microspheres (ASA@CM/SL) by electrospray. ASA@CM/SL safeguards 5-ASA against the harsh gastrointestinal environment and provides favorable delivery to the colon. The anti-inflammatory and anti-oxidant activity is studied by measuring inflammatory factors and reactive oxygen species (ROS). The therapeutic effect of ASA@CM/SL on UC mice induced with dextran sulfate sodium is assessed. The biosafety by evaluating cytotoxicity and organ toxicity is studied. ASA@CM/SL shows excellent therapeutic effects for UC, as evidenced by its alleviation of inflammatory response and restoration of disrupted intestinal barriers. ASA@CM/SL features low cytotoxicity and low organ toxicity. This study provides a potential strategy for improving 5-ASA solubility and delivery efficiency, which may also be applied to broadly tackle various small hydrophobic molecules to treat UC and other intestinal diseases.