Chrysin-nanoencapsulated PLGA-PEG for macrophage repolarization: Possible application in tissue regeneration

The purpose of this study was to investigate the efficiency of a natural flavonoid, Chrysin (Chr), encapsulated in PLGA-PEG nanoparticles (NPs) for the modulation of macrophage polarity from the pro-inflammatory M1 to anti-inflammatory M2 phenotype. The synthetized NPs were characterized using FTIR, DLS and FE-SEM. MTT assay was used to assess the toxicity of different concentration of Chr-encapsulated NPs on LPS/IFN-γ stimulated peritoneal exudate macrophages. To investigate the repolarization efficiency of Chr-encapsulated NPs, real-time PCR was applied to measure M1 (iNOS and SOCS3) and M2 (Arg1 and Fizz) markers expression. Also, the relative mRNA and protein expression levels of pro-inflammatory cytokines including IL-6, IL-1β and TNF-α were investigated in M1 macrophages treated with Chr-encapsulated NPs. Findings revealed that the Chr-encapsulated NPs with spherical shape and an average diameter of 235 nm were considerably less toxic to the macrophages. Additionally, the nano-formulated Chr efficiently showed a reduction in M1 markers and an increase in M2 markers levels than free Chr. Furthermore, macrophage phenotype switching by PLGA-PEG encapsulated Chr NPs significantly suppressed LPS/IFN-γ induced inflammation by a remarkable reduction in pro-inflammatory cytokine levels, TNF-α, IL-1β, and IL-6. Convincingly, the results revealed that PLGA-PEG encapsulated Chr based drug delivery system might be introduced into biomaterials to fabricate bioactive smart multifunctional nanocomposites with macrophage repolarization activities for regenerative medicine purposes.