Biomaterials coating for on-demand bacteria delivery: Selective release, adhesion, and detachment

Abstract

Bacteria-based therapy has shown great promise in treating various diseases by regulating intestinal flora balance in pre-clinical and clinical studies. However, weak resistance against stress in the gastrointestinal (GI) tract and limited retention time in the intestine result in low bacteria availability and persistence, restricting further clinical application. Here, we report a double-layer coating strategy employing tannic acid (TA) and enteric L100 for probiotics encapsulation to address the delivery challenges after oral administration. The Escherichia coli Nissle 1917 (EcN) sequentially encapsulated by TA and L100 layers display robust resistances against the harsh external environment of the GI tract. Furthermore, the pH-responsive degradation of the outer L100 layer leads to the selective delivery of TA-EcN to the intestine, where the strong mucoadhesive capability of the TA layer prolongs the retention time of EcN without compromising the viability and proliferation capabilities of EcN, resulting in superior efficacy of prophylactic and treatment efficacy against colitis. To mitigate the potential side effects caused by long-term mucoadhesion of TA, the TA layer can be further removed by addition of ethylenediaminetetraacetic acid (EDTA). The spatiotemporal delivery of probiotics through double-layer encapsulation can augment the therapeutic efficacy of bacteria-based therapy against GI tract-related diseases.