Delivery of E. coli Nissle to the mouse gut by mucoadhesive microcontainers does not improve its competitive ability against strains linked to ulcerative colitis.

For patients with ulcerative colitis (UC), administration of the probiotic E. coli Nissle (EcN) holds promise for alleviation of disease symptoms. The mechanisms are unclear, but it has been hypothesised that a capacity of the probiotic to outcompete potentially detrimental UC-associated E. coli strains plays an important role. However, this could previously not be confirmed in a mouse model of competition between EcN and two UC-associated strains, as reported by Petersen et al. 2011. In the present study, we re-evaluated the idea, hypothesising that delivery of EcN by a micro device dosing system (microcontainers), designed for delivery into the intestinal mucus, could support colonisation and confer a competition advantage compared to classical oral dosing. Six groups of mice were pre-colonised with one of two UC-associated E. coli strains followed by oral delivery of EcN, either in capsules containing microcontainers with freeze-dried EcN powder, capsules containing freeze-dried EcN powder, or as a fresh sucrose suspension. Co-colonisation between the probiotic and the disease-associated strains was observed regardless of dosing method, and no competition advantages linked to microcontainer delivery were identified within this setup. Other approaches are thus needed if the competitive capacity of EcN in the gut should be improved.

Open source anaerobic and temperature-controlled in vitro model enabling real-time release studies with live bacteria.

In vitro release and dissolution models are widely used in the development phases of oral drug delivery systems to measure how an active pharmaceutical ingredient (API) is released from a dosage form. However, additional requirements for these models arise when evaluating probiotic dosage forms since they are often sensitive to temperature and oxygen levels. As a solution to this, we propose a custom-designed anaerobic in vitro release setup, made mainly by 3D printing and laser cutting, to function together with state-of-the-art pharmaceutical dissolution equipment - in this case, a microDISS Profiler™. The in vitro release model makes it possible to study the release rate of oxygen-sensitive probiotics in simulated intestinal conditions, while ensuring their survival due to the anaerobic conditions. This has not been possible so far since the available in vitro dissolution models have not been compatible with anaerobic conditions. With two different case studies, the developed model combined with a microDISS Profiler™ has proven capable of measuring the release of a probiotic and a small-molecule API from microdevices for oral drug delivery. Further, the model facilitated the survival of anaerobic bacteria present in the release medium.