Electrospun Solid Formulation of Anaerobic Gut Microbiome Bacteria
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Research Article Electrospun Solid Formulation of Anaerobic Gut Microbiome Bacteria Panna Vass,1 Eszter Pantea,1 András Domokos,1 Edit Hirsch,1 Júlia Domján,1 Áron Németh,2 Mónika Molnár,2 Csaba Fehér,2 Sune K. Andersen,3 Tamás Vigh,3 Geert Verreck,3 István Csontos,1 György Marosi,1 and Zsombor K. Nagy1,4
Received 4 May 2020; accepted 21 July 2020 Abstract.
A model anaerobic bacterium strain from the gut microbiome (Clostridium butyricum) producing anti-inflammatory molecules was incorporated into polymer-free fibers of a water-soluble cyclodextrin matrix (HP-β-CD) using a promising scaled-up nanotechnology, high-speed electrospinning. A long-term stability study was also carried out on the bacteria in the fibers. Effect of storage conditions (temperature, presence of oxygen) and growth conditions on the bacterial viability in the fibers was investigated. The viability of the sporulated anaerobic bacteria in the fibers was maintained during 12 months of room temperature storage in the presence of oxygen. Direct compression was used to prepare tablets from the produced bacteria-containing fibers after milling (using an oscillating mill) and mixing with tableting excipients, making easy oral administration of the bacteria possible. No significant decrease was observed in bacterial viability following the processing of the fibers (milling and tableting). KEY WORDS: aqueous electrospinning; scaled-up production; cyclodextrin; bacteria-loaded fibers; oral dosage form.
INTRODUCTION Since the start of the Human Microbiome Project in 2008, it has become evident that the microbes that live in the human body—called the microbiome—play critical roles in biological processes, including intestinal homeostasis, metabolism, and development of the immune system, among others (1). Composition changes in the intestinal microbiota have been correlated to diverse, complex diseases including metabolic diseases (diabetes, obesity), inflammatory bowel disease, allergy, asthma, cancer, and neurologic and cardiovascular diseases (2). Based on these links, numerous pharmaceutical companies started to focus on the development of microbiome therapeutics (3,4). Defined bacterial consortia—generally consisting of 2 to 20 different bacterial strains—have been shown to enable the tailored manipulation of the microbiome, making it possible to use them as effective biotherapeutics (5,6). The manufacturing of such drugs is a 1
Department of Organic Chemistry and Technology, Budapest University of Technology and Economics (BME), Műegyetem rakpart 3, Budapest, H-1111, Hungary. 2 Department of Applied Biotechnology and Food Science, Budapest University of Technology and Economics (BME), Műegyetem rakpart 3, Budapest, H-1111, Hungary. 3 Oral Solids Development, Janssen R&D, Turnhoutseweg 30, B2340, Beerse, Belgium. 4 To whom correspondence should be addressed. (e–mail: [email protected])
great challenge since fermentation and solid formulation needs to be developed separately for each strain, which means that the development times and costs are multiplied by
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