Simvastatin nanoparticles reduce inflammation in LPS-stimulated alveolar macrophages

Alaa S. Tulbah, Elvira Pisano, Emelie Landh, Santo Scalia, Paul M. Young, Daniela Traini, Hui Xin Ong*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Simvastatin (SV) is widely used as a lipid-lowering medication that has also been found to have beneficial immunomodulatory effects for treatment of chronic lung diseases. Although its anti-inflammatory activity has been investigated, its underlying mechanisms have not yet been clearly elucidated. In this study, the anti-inflammatory and antioxidant effects and mechanism of simvastatin nanoparticles (SV-NPs) on lipopolysaccharide-stimulated alveolar macrophages (AMs) NR8383 cells were investigated. Quantitative cellular uptake of SV-NPs, the production of inflammatory mediators (interleukin-6, tumor necrosis factor, and monocyte chemoattractant protein-1), and oxidative stress (nitric oxide) were tested. Furthermore, the involvement of the nuclear factor κB (NF-κB) signaling pathway in activation of inflammation in AMs and the efficacy of SV were visualized using immunofluorescence. Results indicated that SV-NPs exhibit a potent inhibitory effect on nitric oxide production and secretion of inflammatory cytokine in inflamed AM, without affecting cell viability. The enhanced anti-inflammatory activity of SV-NPs is likely due to SV-improved chemical-physical stability and higher cellular uptake into AM. The study also indicates that SV targets the inflammatory and oxidative response of AM, through inactivation of the NF-κB signaling pathway, supporting the pharmacological basis of SV for treatment of chronic inflammatory lung diseases.

Original languageEnglish
Pages (from-to)3890-3897
Number of pages8
JournalJournal of Pharmaceutical Sciences
Volume108
Issue number12
DOIs
Publication statusPublished - Dec 2019
Externally publishedYes

Keywords

  • anti-inflammation
  • inhalation
  • NF-κB
  • NR8383 cells
  • simvastatin nanoparticles

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