Macrophage repolarization using CD44-targeting hyaluronic acid-polylactide nanoparticles containing curcumin

Artif Cells Nanomed Biotechnol. 2018 Dec;46(8):2013-2021. doi: 10.1080/21691401.2017.1408116. Epub 2017 Nov 28.


The aim of this study was to evaluate the efficiency of using a natural substance, curcumin, encapsulated in CD44-targeting hyaluronate-polylactide (HA-PLA) nanoparticles (NPs) for the modulation of macrophage polarity from the pro-inflammatory M1 to anti-inflammatory M2 phenotype. For this purpose, the characterization of the NPs was monitored using 1HNMR, FTIR, DLS and FE-SEM. The effects of curcumin-encapsulated HA-PLA NPs on the viability of LPS/IFN-γ stimulated peritoneal macrophages were determined using MTT assay. The cellular uptake of free curcumin and nano-formulated curcumin was assessed using confocal microscopy. Also, the expression levels of iNOS-2 (M1 marker), Arg-1 (M2 marker) and also pro-inflammatory cytokines were measured by real-time PCR. Data showed that the nano-formulated curcumin with spherical shape, an average diameter of 102.5 nm and high cellular uptake was significantly less toxic to peritoneal macrophages. Furthermore, the nano-formulated curcumin effectively indicated a reduction in iNOS-2 and an increase in Arg-1 levels than free curcumin. The change in macrophage phenotype by curcumin-encapsulated HA-PLA NPs could suppress the inflammation in LPS/IFN-γ stimulated macrophages as evidenced by a major reduction in pro-inflammatory cytokines. Conclusively, the results suggested that the curcumin formulation with CD44-targeting HA-PLA NPs might be a promising platform for the treatment of inflammatory diseases.

Keywords: Curcumin; hyaluronic acid; inflammation; macrophage polarity; nanoparticles.

MeSH terms

  • Animals
  • Cell Polarity / drug effects*
  • Curcumin* / chemistry
  • Curcumin* / pharmacology
  • Drug Delivery Systems / methods*
  • Gene Expression Regulation / drug effects
  • Hyaluronan Receptors / metabolism*
  • Hyaluronic Acid* / chemistry
  • Hyaluronic Acid* / pharmacology
  • Macrophages, Peritoneal / metabolism*
  • Macrophages, Peritoneal / pathology
  • Mice
  • Nanoparticles / chemistry*


  • Cd44 protein, mouse
  • Hyaluronan Receptors
  • Hyaluronic Acid
  • Curcumin