Lipid Nanostructures Containing Atorvastatin Decrease Lipopolysaccharide-Induced Inflammation in Macrophages
Atorvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, is known to exert lipid-lowering, but also anti-inflammatory effects in extra-arterial locations. In order to avoid its toxicity associated with long-term oral treatment, in this study we have proposed novel
lipid nanostructures containing atorvastatin to improve its efficiency and bioavailability after local application in periodontitis inflammation therapy. The physico-chemical characterization of the nanostructures was performed using dynamic light scattering technique and morphological observations
were made by light microscopy. The encapsulation efficiency was determined by high performance liquid chromatography analysis of loaded atorvastatin. In vitro cytotoxicity and anti-inflammatory activity were evaluated in human premonocytic THP-1 cell line and a model of lipopolysaccharide-induced
inflammation in macrophages, respectively. The results showed that the population of atorvastatin lipid nanostructures presented a mean diameter of 178 nm and a good homogeneity after sonication and extrusion treatments applying, as indicated by the low polydispersity index of 0.223. The efficiency
of atorvastatin encapsulation was high (87.3%) and the nanostructures cytotoxicity was reduced for lipid concentrations ranging from 50 μM to 500 μM. Experiments in THP-1 cells differentiated to macrophages demonstrated that atorvastatin liposomal formulation led to a higher
inhibition of lipopolysaccharide-induced proinflammatory cytokines (interleukin 6, tumor necrosis factor alpha and interleukin 8) release, compared to free drug. In conclusion, atorvastatin lipid nanostructures could be used to develop an efficient local treatment of periodontitis inflammation.
Document Type: Research Article
Institute of Biochemistry of the Romanian Academy, 296, Splaiul Independentei, Sector 6, 060031 Bucharest, Romania
National Institute of Research and Development for Biological Sciences, 296, Splaiul Independentei, Sector 6, 060031 Bucharest, Romania
July 1, 2017
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