Designing an Ingestible Encapsulated Therapeutic for Resolving Recurrent Clostridioides difficile Infection; Investigating the Historical and Social Reasons Behind the Stagnation and Failures in Clostridioides difficile Treatments

Shekharan, Swathi, School of Engineering and Applied Science, University of Virginia
Papin, Jason, MD-BIOM Biomedical Eng, University of Virginia
Allen, Timothy, EN-Biomed Engr Dept, University of Virginia
Forelle, MC, Engineering and Society, University of Virginia
Kolling, Glynis, MD-BIOM Biomedical Eng, University of Virginia

Clostridioides difficile infection (CDI) poses a significant healthcare challenge, characterized by high recurrence rates and limited treatment options. This study aims to address this issue by proposing the development of an encapsulated biologic of cooperative bacteria as a novel therapeutic approach for CDI. Using computational modeling, a consortium of bacteria comprising Bifidobacterium longum ATCC 55813, Escherichia coli K12, Roseburia intestinalis DSM 14610, and Streptococcus thermophilus LMD-99 was previously identified as effective in combating CDI while preserving the gut microbiota. Subsequently, a method for the encapsulation of these bacteria in a biocompatible hydrogel matrix of norbornene-functionalized carboxymethylcellulose (cCMC) was developed and optimized to ensure stability and efficacy under physiologically relevant conditions. Stability studies, including exposure to varying pH levels, temperature, and enzymatic degradation, demonstrated the viability of encapsulated bacteria over time. Notably, the encapsulation method exhibited minimal degradation in acidic conditions mimicking the gastrointestinal tract. Future work will focus on refining encapsulation methods, optimizing the bundling matrix for ease of ingestion, and conducting further degradation studies to confirm the biologic's efficacy of release in the large intestine. Overall, the development of an encapsulated biologic offers a promising advancement in CDI therapeutics, with the potential to introduce new, improved treatment outcomes and alleviate the burden of this persistent healthcare challenge.

BS (Bachelor of Science)
Carboxymethylcellulose, CDI, Stagnation, Inertia
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