Delivery of Encapsulated Intelligent Engineered Probiotic for Inflammatory Bowel Disease Therapy

Abstract Engineered bacterial therapy holds enormous potential for treating intestinal diseases, employing synthetic biology techniques to achieve localized drug delivery within intestines. However, effective delivery of engineered bacteria to lesion sites and ensuring sustained colonization remain challenging. Here, a mucus encapsulated microsphere gel (MM) delivery system is developed to encapsulate genetically engineered bacteria capable of detecting and treating enteritis. The MM delivery system features an external mucosal coating composed of hyaluronic acid and epigallocatechin gallate, along with internal microspheres of highly biocompatible polyserine modified alginates encapsulating with the engineered probiotics. The MM delivery system effectively protects engineered bacteria harsh environment in stomach and significantly improves intestinal adhesion of the probiotics, extending colonization up to 24 h, and does not affect the entry of biomarker or release of Avcystatin. It exhibits notable diagnostic and therapeutic efficacy in inflammatory bowel disease models, thus facilitating the advancement of live biotherapeutic products toward clinical application.