Farnesol-Loaded Nanoliposomes Inhibit Inflammatory Gene Expression in Primary Human Skeletal Myoblasts

Abstract

There is a substantial unmet need for the treatment of skeletal muscle mass loss that is associated with aging and obesity-related increases in FFA. Unsaturated FFAs stimulate the inflammatory gene expression in human skeletal myoblasts (SkMs). Farnesol is a hydrophobic acyclic sesquiterpene alcohol with potential anti-inflammatory effects. Here, we created farnesol-loaded small unilamellar (SUVs) or multilamellar lipid-based vesicles (MLVs), and investigated their effects on inflammatory gene expression in primary human skeletal myoblasts. The attachment of SUVs or MLVs to SkMs was tracked using BODIPY, a fluorescent lipid dye. The data showed that farnesol-loaded SUVs reduced FFA-induced IL6 and LIF expression by 77% and 70% in SkMs, respectively. Farnesol-loaded MLVs were less potent in inhibiting FFA-induced IL6 and LIF expression. In all experiments, equal concentrations of free farnesol did not exert significant effects on SkMs. This report suggests that farnesol, if efficiently directed into myoblasts through liposomes, may curb FFA-induced inflammation in human skeletal muscle.

Farnesol Inhibits PI3 Kinase Signaling and Inflammatory Gene Expression in Primary Human Renal Epithelial Cells

“…The PDIs of farnesol-SUV and SUV differed by 0.057, which is negligible according to the DSL standards [19]. The efficiency of farnesol encapsulation was 3.926 mM (98.15%), determined by reverse-phase high-performance liquid chromatography (HPLC), as described previously [18].…”

“…PC and DOTAP (Avanti Polar Lipids Inc., Alabaster, AL, USA) were utilized in 98:2% molar ratios to prepare liposomes with or without adding 4 mM farnesol (Sigma-Aldrich, Inc., St. Louis, MO, USA) using the lipid film hydration method [18]. All components were solved in chloroform and mixed thoroughly for 5 min.…”

“…The resulting liposomal suspension was sonicated (Sonic Dismembrator Model 100, 1β (Fisher Scientific, Pittsburgh, PA, USA) at 5 W for 45 min in an ice bath to obtain the SUVs. Titanium particles resulting from sonication were removed by centrifugation at 1550× g (RCF) for 15 min at 4 • C. The encapsulation efficiency of farnesol was 98.15% as determined by reverse-phase high-performance liquid chromatography (HPLC) analysis, as described previously [18]. A Nano ZS Zetasizer (Malvern Panalytical, Westborough, MA, USA) was used to measure the hydrodynamic diameters of the liposomes in triplicate via dynamic light scattering (DLS) at 25 • C. The results were reported as size by volume (nm) and polydispersity index in this study.…”

“…In a previous study in human skeletal myoblasts, we previously established a procedure for the encapsulation of farnesol in SUVs composed of DOTAP and PC/soy [18]. For the current study, we followed the same formula and created two batches of SUVs, one with farnesol (farnesol-SUV) and one without farnesol (SUV).…”

“…Recently, we encapsulated farnesol in small unilamellar vesicles (SUVs) consisting of the phospholipid L-α-phosphatidylcholine (PC) and the lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP). These SUVs have been successfully applied to human skeletal myoblasts [18]. The aim of the current study was to examine the effect of farnesol-SUVs on the inflammatory response of primary human RPTECs and to identify the target genes and signaling factors of farnesol that may be relevant to renal inflammation and CKD.…”