3D printed pH-responsive colonic capsules for the delivery of live aqueous bacterial suspensions

Delivering live bacterial therapeutics orally to the colon is challenging due to the harsh gastrointestinal (GI) conditions and/or the manufacturing processes involved in the production of dry formulations, which can drastically decrease cell viability. In a previous work, we evaluated the performance of a 3D printed pHresponsive capsule capable of encapsulating aqueous cargos. We herein evaluate its ability to encapsulate live bacterial suspensions with limited processing steps. The capsules maintained their integrity in conditions simulating the upper GI tract (stomach and proximal intestine) and only released their contents in the environment of the lower intestine, i.e., ileum and colon. The mean viability of individual or mixed selected strains remained above 75% during a full simulated GI transit to the colon. In beagle dogs, genomic DNA of 2 out of the 3 delivered strains was detected in the feces, and DNA copy levels did not differ between the capsules and the control suspension of non-encapsulated bacteria. These results could be attributed to the differing physiological conditions of fasted beagle dogs vs. the simulated environments, or possibly to a non-optimal assessment of bacterial colonization. A follow-up study after capsule treatment, incorporating sampling from various colonic tissues and fluids, could provide some insights into bacterial colonization process.