Modulating pro-fibrotic macrophages using yeast beta-glucan microparticles prepared by Pressurized Gas eXpanded liquid (PGX) Technology

• Published in: Biomaterials Vol. 313; p. 122816
• Main Authors: Naiel, S., Dowdall, N., Zhou, Q., Ali, P., Hayat, A., Vierhout, M., Wong, E.Y., Couto, R., Yépez, B., Seifried, B., Moquin, P., Kolb, M.R., Ask, K., Hoare, T.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-02-2025
• ISSN: 0142-9612; 1878-5905; 1878-5905
• DOI: 10.1016/j.biomaterials.2024.122816

Pro-fibrotic M2-like macrophages are widely implicated in the pathogenesis and progression of lung fibrosis due to their production of pro-fibrotic growth factors and cytokines. Yeast beta-glucan (YBG) microparticles have shown potential as immunomodulators that can convert macrophage polarization from a pro-fibrotic phenotype to an anti-fibrotic phenotype through the engagement of the Dectin-1 receptor. However, the processing conditions used to fabricate YBG microparticles can lead to unpredictable immunomodulatory effects. Herein, we report the use of Pressurized Gas eXpanded liquids (PGX) Technology® to fabricate YBG (PGX-YBG) microparticles with higher surface areas, lower densities, and smaller and more uniform size distributions compared to commercially available spray-dried YBGs. PGX-YBG is shown to activate Dectin-1 more efficiently in vitro while avoiding significant TLR 2/4 activation. Furthermore, PGX-YBG microparticles effectively modulate M2-like fibrosis-inducing murine and human macrophages into fibrosis-suppressing macrophages both in vitro as well as in ex vivo precision-cut murine lung slices, suggesting their potential utility as a therapeutic for addressing a broad spectrum of fibrotic end-point lung diseases.
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•Scalable production of high purity, highly porous yeast beta-glucan (PGX-YBG) microparticles.•Enhanced Dectin-1 activation compared to conventional spray dried YBG.•PGX-YBG preferentially taken up by pro-fibrotic macrophages.•Effective immunomodulation of human and murine macrophages in vitro and ex vivo.•Particle properties are conducive to effective lung delivery via inhalation.