Broad-Spectrum ROS/RNS Scavenging Catalase-Loaded Microreactors for Effective Oral Treatment of Inflammatory Bowel Diseases

Abstract

Inflammatory bowel disease (IBD) such as ulcerative colitis (UC) is an autoimmune disease characterized by persistent inflammation along the gastrointestinal tract with excessive generation of reactive oxygen species (ROS)/reactive nitrogen species (RNS) generation. Here, catalase (CAT)-containing microreactor capsules with long-lasting broad-spectrum ROS/RNS-scavenging capability are developed for the treatment of IBD. In this design, CAT is encapsulated in the dense hydrogel network of calcium alginate (ALG) microspheres, which provides long-term protection of CAT activity in protease-rich intestinal environment. Afterward, the polydopamine (PDA) modification on the surface of CAT@ALG microspheres can provide them bioadhesiveness to achieve prolonged retention in the intestinal tract and broad-spectrum scavenging capability against various types of ROS/RNS beyond hydrogen peroxide. Enteric capsules are further used to protect the CAT@ALG–PDA microspheres from gastric fluid for selective release at the intestinal site. The combined action of PDA and CAT in CAT@ALG–PDA microreactors results in the broad-spectrum scavenging of excess ROS/RNS and regulates redox balance in acute UC rat model, showing satisfactory therapeutic effects superior to the mesalazine and adalimumab at clinically relevant doses without obvious side effects. This work highlights that these CAT@ALG–PDA capsules can act as long-acting broad-spectrum ROS/RNS reactors, promising for IBD treatment.