Simvastatin Nanoparticles Reduce Inflammation in LPS-Stimulated Alveolar Macrophages

• Published in: Journal of pharmaceutical sciences 2019-12, Vol.108 (12), p.3890-3897
• Main Authors: Tulbah, Alaa S., Pisano, Elvira, Landh, Emelie, Scalia, Santo, Young, Paul M., Traini, Daniela, Ong, Hui Xin
• Format: Article
• Language: English
• Subjects: anti-inflammation; inhalation; NF-κB; NR8383 cells; simvastatin nanoparticles
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1016/j.xphs.2019.08.029

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.