Novel pharmaco-exosomal immunotherapy for united airway diseases: PLGA-encapsulated, mesenchymal stem cell-derived exosomes with PPAR-γ agonist for allergic rhinitis and asthma.

BACKGROUND

The united airway diseases (UADs), exemplified by allergic rhinitis and asthma, cause significant morbidity. Although conventional pharmacotherapy provides symptomatic relief, recent evidence has indicated that cellular therapy, such as stem cell-derived exosomes, might offer therapeutic advantages throughout the entire respiratory tract.

OBJECTIVES

The present study intends to demonstrate the effect and explore the mechanism of a novel pharmaco-exosomal immunotherapy, i.e., mesenchymal stem cells-derived exosomes (MSC-exo) supplemented with PPAR-γ agonists (Pioglitazone), which is locally delivered using PLGA nanoparticles (PLGA-exo-PIO) for the treatment of allergic airway diseases using male Balb/c mice.

METHODS

The in vitro and in vivo therapeutic potential was observed using fluorescence imaging, RT-qPCR, ELISA, histopathology, flow cytometry, and bioinformatics analysis.

RESULTS

Our results indicated that PLGA NPs exhibited prolonged retention and sustained release in the nasal cavity and lungs. In vitro, PLGA-exo-PIO treatment suppresses LPS-induced inflammation in nasal epithelial cells and mast cells. Using murine models of UADs, PLGA-exo-PIO therapy significantly improved the symptom score, reduced inflammatory cells (i.e., eosinophils and goblets) at tissue levels, and upregulated IFN-γ and IL-10 while downregulating histamine, IgE, LTC4, IL-4, and IL-17. In addition, flow cytometric analysis revealed elevated counts of Th1 cells, Tregs, and Bregs, and reduced Th2 cells, eosinophils, and basophils in the blood and spleen of the treated mice. Finally, the data from bioinformatic analysis supported the therapeutic capabilities of fabricated PLGA-exo-PIO via regulation of multiple signaling pathways, such as the Notch cascade and NF-kB cascade.

CONCLUSION

For the first time, we used a PLGA-delivered, PIO-strengthened MSC-exo system (PLGA-exo-PIO) as a novel therapy to simultaneously manage AR and asthma as UADs.