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Modulation of macrophage phenotype via phagocytosis of drug‐loaded microparticles
Author(s) -
Wofford Kathryn L.,
Cullen D. Kacy,
Spiller Kara L.
Publication year - 2019
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.36617
Subject(s) - phagocytosis , macrophage , phenotype , microbiology and biotechnology , monocyte , macrophage activating factor , materials science , downregulation and upregulation , inflammation , biology , immunology , in vitro , gene , biochemistry
Monocyte‐derived macrophages play a critical role in directing wound pathology following injury. Depending on their phenotype, macrophages also promote tissue regeneration. However, the therapeutic administration of macrophages with a controlled phenotype is challenging because macrophages are highly plastic and quickly revert to a detrimental, inflammatory phenotype in response to the environment of a damaged tissue. To address this issue, we developed a novel strategy to modulate macrophage phenotype intracellularly through phagocytosis of drug‐loaded microparticles. Poly(lactic‐co‐glycolic acid) microparticles loaded with the anti‐inflammatory drug dexamethasone (Dex) were phagocytosed by monocytes and stored intracellularly for at least 5 days. After differentiation into macrophages, cell phenotype was characterized over time with high‐throughput gene expression analysis via NanoString. We found that the microparticles modulated macrophage phenotype for up to 7 days after microparticle uptake, with decreases in inflammation‐related genes at early timepoints and upregulation of homing‐ and phagocytosis‐related genes at multiple timepoints in a manner similar to cells treated with continuous free Dex. These data suggest that intracellularly loading macrophages with Dex microparticles via phagocytosis could be a unique methodology to selectively modulate macrophage phenotype over time. This strategy would allow therapeutic administration of macrophages for the treatment of a number of inflammatory disease and disorders. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1213–1224, 2019.