Lipid Nanostructures Containing Atorvastatin Decrease Lipopolysaccharide-Induced Inflammation in Macrophages

Abstract

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.

Impact of local drug delivery and natural agents as new target strategies against periodontitis: new challenges for personalized therapeutic approach

“…The results showed a decrease of lipopolysaccharide inducedproinflammatory cytokines Moisei et al 81 Chitosan and hyaluronic acid…”

“…Moisei et al 81 formulated liposomes packed with atorvastatin and studied the efficacy after their local administration in human macrophages cells culture. The results showed a larger decrease of lipopolysaccharide-induced-proinflammatory cytokines concentration in the cells culture treated with atorvastatin loaded on liposomes [74% inhibition of IL-6, 48% inhibition of Tumor Necrosis Factor (TNF), and 56% inhibition of IL-8] compared to the control group in which atorvastatin alone was administered (54% inhibition of IL-6, 36% inhibition of TNF, and 26% inhibition of IL-8).…”

Liposomal nanocarriers for statins: A pharmacokinetic and pharmacodynamics appraisal

“…In addition to its lipid-lowering effect, another important attribute of atorvastatin (ATV) is its anti-inflammatory properties in extra-arterial sites. Moisei, Craciunescu, Moldovan, Roseanu, and Trif (2017) reported a new formulation of ATV liposomes that increase its bioavailability and efficiency in local treatment of periodontal tissue inflammation. According to biocompatibility testing, the cytotoxicity associated with the nanostructure was not observed in the range of 50-300 µM lipid concentration.…”

“…Comparing free ATV, empty liposomes and ATV liposomal formulation showed that the highest inhibition of tumor necrosis factor-α, interleukin (IL)-6, and IL-8 secretion was observed in the presence of the ATV liposomal formulation. Thus, liposomal formulation may improve the ATV anti-inflammatory effect and this is a promising strategy for local treatment of periodontitis inflammation (Moisei et al, 2017).…”