Inhalability and Bioactivity of Spray-Dried versus Pressurized Gas eXpanded Liquid Technology-Processed Yeast Beta-Glucan Microparticles for Anti-Fibrotic Therapies.

Current anti-fibrotic therapeutics for idiopathic pulmonary fibrosis (IPF) slow disease progression but are non-curative and have systemic side effects, promoting interest in therapies that can repolarize macrophages away from their pro-fibrotic phenotype. While yeast beta-glucan (YBG) offers therapeutic potential in reprogramming macrophages toward an anti-fibrotic phenotype, YBG processing must be optimized to promote inhalability while preserving its biological activity. Herein, the biological and inhalation performance of YBG processed via Pressurized Gas eXpanded liquids technology (PGX(TEC)-YBG) relative to conventionally spray-dried YBG (SD-YBG) is compared. The significantly smaller size and lower density of PGX(TEC)-YBG relative to SD-YBG result in a smaller aerodynamic diameter (3-4 µm) and double the fine particle fraction in cascade impaction studies, variables correlated with improved inhalability and thus deposition in the distal regions of the lung. Correspondingly, PGX(TEC)-YBG shows an approximately double phagocytic index in vitro and enhanced suppression of CD206 expression and arginase-1 activity, lower levels of macrophage stress, and comparable capacity for promoting pro-inflammatory cytokine release in ex vivo murine precision cut lung slices relative to SD-YBG. These findings highlight PGX(TEC)-YBG's utility as a promising inhalable therapeutic that can offer improved delivery to the disease site while maintaining strong biological anti-fibrotic effects and reduced systemic toxicity.