| L-carnitine (LC) is a highly water-soluble compound involved in the β-oxidation of lipids and transportation of
long-chain fatty acids across the membrane of mitochondria. However, the higher hydrophilicity of LC limits its
free diffusion across the bilayer lipid membrane of intestinal epithelium in oral administration, decreasing oral
bioavailability. Drug delivery with nanoparticles enhances cargo bioavailability and cellular uptake and improves therapeutic outcomes while decreasing unwanted side effects. Here, we proposed solid lipid nanoparticles
(SLNs) as a hydrophobic carrier for LC delivery, aiming at increasing LC bioavailability and its protective role
against intracellular oxidative stress damages. The LC-SLNs were prepared using the hot homogenization technique, and different physicochemical properties were investigated. The inhibition of H2O2-induced ROS generation in human umbilical vein endothelial cells (HUVECs) with plain LC and LC-SLNs was investigated.
Moreover, various in vitro experiments were performed to assess whether LC-SLNs can protect HUVECs from
H2O2-induced genotoxicity and apoptosis. The monodispersed and spherical blank SLNs and LC-SLNs were 104
± 1.8 and 128 ± 1.5 nm, respectively with a drug loading (DL) of 11.49 ± 0.78 mg/mL and acceptable
encapsulation effciency (EE%) (69.09 ± 1.12) of LC-SLNs. The formulation process did not affect the antioxidant
properties of LC. MTT assay and comet assay demonstrated that the LC-SLNs decreased cytotoxicity and genotoxicity of H2O2, respectively on HUVECs. Besides, LC-SLNs more inhibited ROS generation, along with apoptotic
events in H2O2-treated HUVECs compared to the plain LC. Altogether, our fndings affrmed the protective effects
of LC-SLNs against H2O2-induced genotoxicity and apoptosis in HUVECs. In conclusion, LC-SLN formulation is a
promising drug delivery system to overcome the bioavailability issue of hydrophilic LC, enhancing the antioxidant and biological properties of the plain LC. |