Commensal Biocapsules as a Bacterial Delivery System to Reengineer the Microbiome
Open Access
- Author:
- Ali, Yasmin
- Area of Honors:
- Biomedical Engineering
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Scott H Medina, Thesis Supervisor
Justin Lee Brown, Thesis Honors Advisor - Keywords:
- biomaterials
microbiome engineering
precision therapy
drug delivery
antimicrobial peptides
gastrointestinal disease - Abstract:
- Antibiotic resistance poses a major cause for concern in the medical treatment of bacterial infections, as it emerges through the accumulation of resistance genes in drug-exposed flora of the gastrointestinal (GI) tract. In particular, the GI pathogen C. difficile exemplifies a common hospital-acquired infection that colonizes the dysbiotic gut resulting from antibiotics. Treatment of this deadly pathogen requires both the removal of the microbe and the reestablishment of the native, healthy microflora of the gut. To address these demands, this research presents a model for commensal-loaded biocapsules that not only possess an antimicrobial coating to clear pathogenic bacteria, but can also reflourish the environment with a defined consortium of encapsulated microorganisms known to support GI health. Characterization studies were used to investigate the formulation of the particles, for which it is hypothesized that hyaluronic acid (HA) from the core reacts with a positively charged antimicrobial agent in solution to form the outer antimicrobial coating, termed the “corona.” The stability of the formulation has also been proven by investigating the biocapsule structure in gastrointestinal fluids. Antimicrobial screenings in four model gastrointestinal pathogens identified an optimal coating formulation, while capsule construction was refined to support the encapsulation of E. coli as a model commensal. Additionally, computational studies have been developed to expand both structural characterization and bacterial-loading models. Overall, these studies have been central to the development of a novel biocapsule therapy for the treatment of gastrointestinal infections like C. difficile in preparation for preclinical studies.