Effects of Microparticle Composition on Colony Morphology and Viability of Encapsulated Therapeutic Yeast for Oral Delivery

Abstract

Engineered live biotherapeutic products (LBPs) offer a promising avenue for targeted drug delivery, particularly within the gastrointestinal (GI) tract. Among microbial chassis, Saccharomyces cerevisiae (S. cerevisiae) is recognized as a highly favorable platform due to its safety profile, genetic amenability, and potential for dual functionality as both a therapeutic protein producer and probiotic. However, oral delivery of LBPs remains challenging due to the harsh conditions of the GI tract, which compromise microbial viability and therapeutic efficacy. To address this, we developed alginate-based hydrogel particles designed to encapsulate S. cerevisiae for oral administration and systematically evaluated their performance under simulated physiological conditions. Notably, we demonstrated that colony size can be tuned through specific alginate formulations, and that colony morphology significantly influences cell survival. Our findings establish key design principles for optimizing hydrogel carriers to enhance the viability and therapeutic potential of engineered microbial therapeutics.