• Biogenic and Biomimetic Carriers as Versatile Transporters To Treat Infections.

      Goes, Adriely; Fuhrmann, Gregor; HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany. (American Chemical Society, 2018-03-29)
      Biogenic and biomimetic therapeutics are a relatively new class of systems that are of physiological origin and/or take advantage of natural pathways or aim at mimicking these to improve selective interaction with target tissue. The number of biogenic and bioengineered avenues for drug therapy and diagnostics has multiplied over the past years for many applications, indicating the high expectations associated with this biological route. Nevertheless, the use of "bio"-related approaches for treating or diagnosing infectious diseases is still rare. Given that infectious diseases, in particular bacterial resistances, are seriously on the rise, there is an urgent need to take advantage of biogenic and bioengineered systems to target these challenges. In this manuscript, we first give a definition of the various "bio" terms, including biogenic, biomimetic, bioinspired, and bioengineered and we highlight them using tangible applications in the field of infectious diseases. Our examples cover cell-derived systems, including bioengineered bacteria, virus-like particles, and different cell-mimetics. Moreover, we discuss natural and bioengineered particles such as extracellular vesicles from mammalian and bacterial sources and liposomes. A concluding section outlines the potential for biomaterial-related avenues to overcome challenges associated with difficult-to-treat infections. We critically discuss benefits and risks for these applications and give an outlook on the future of biogenic engineering.
    • Probiomimetics-Novel Lactobacillus-Mimicking Microparticles Show Anti-Inflammatory and Barrier-Protecting Effects in Gastrointestinal Models.

      Kuhn, Thomas; Koch, Marcus; Fuhrmann, Gregor; HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany. (Wiley, 2020-09-03)
      There is a lack of efficient therapies to treat increasingly prevalent autoimmune diseases, such as inflammatory bowel disease and celiac disease. Membrane vesicles (MVs) isolated from probiotic bacteria have shown tremendous potential for treating intestinal inflammatory diseases. However, possible dilution effects and rapid elimination in the gastrointestinal tract may impair their application. A cell‐free and anti‐inflammatory therapeutic system—probiomimetics—based on MVs of probiotic bacteria (Lactobacillus casei and Lactobacillus plantarum) coupled to the surface of microparticles is developed. The MVs are isolated and characterized for size and protein content. MV morphology is determined using cryoelectron microscopy and is reported for the first time in this study. MVs are nontoxic against macrophage‐like dTHP‐1 and enterocyte‐like Caco‐2 cell lines. Subsequently, the MVs are coupled onto the surface of microparticles according to facile aldehyde‐group functionalization to obtain probiomimetics. A significant reduction in proinflammatory TNF‐α level (by 86%) is observed with probiomimetics but not with native MVs. Moreover, it is demonstrated that probiomimetics have the ability to ameliorate inflammation‐induced loss of intestinal barrier function, indicating their potential for further development into an anti‐inflammatory formulation. These engineered simple probiomimetics that elicit striking anti‐inflammatory effects are a key step toward therapeutic MV translation.