Developing a topical administration system to support engineered probiotics in addressing pathogenic microbial overgrowth

Skin disorders are of high prevalence, with acne affecting up to 50 million people in the US annually and psoriasis affecting 2% of the global population. Factors such as environmental triggers, side effects of medication, and lifestyle choices have been researched for their connection to skin condition occurrence, but skin microbial dysbiosis (disruption of the microbial community associated with the skin) is a factor of increasing scientific value. The microbiome of patients with skin conditions have been found to have imbalance of bacterial and fungal species, providing motivation for therapies that address microbial dysbiosis in skin conditions. My thesis investigated drug delivery systems for loaded yeast: being loaded into a cream with various additives, and being encapsulated in alginate-based biospheres and then mixed into a base cream. Results show that a yeast pellet loaded into a cream with hyaluronic acid or inulin had the highest microbial viability, and yeast showed growth when encapsulated in biospheres and the spheres were mixed in cream. The enzyme lysostaphin was also investigated in its ability to be engineered to be displayed by S. boulardii, serving as an engineered live biotherapeutic for the skin. My thesis proves that topical administration systems can successfully be loaded with yeast while retaining viability, and that bacteria can be successfully engineered to have the lysostaphin gene; this proves the potential for microbial-based therapeutics in skin applications.