Department of Animal Science, Faculty of Agriculture and Natural Resources, University of Mohaghegh Ardabili, Ardabil, Iran.
Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
Colloids Surf B Biointerfaces. 2022 Apr;212:112365. doi: 10.1016/j.colsurfb.2022.112365. Epub 2022 Jan 29.
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 HO-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 HO-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 efficiency (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 HO, respectively on HUVECs. Besides, LC-SLNs more inhibited ROS generation, along with apoptotic events in HO-treated HUVECs compared to the plain LC. Altogether, our findings affirmed the protective effects of LC-SLNs against HO-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.
左旋肉碱（LC）是一种高度水溶性化合物，参与脂质的β氧化和长链脂肪酸穿过线粒体膜的运输。然而，LC 的较高亲水性限制了其在口服给药时通过肠上皮细胞双层脂质膜的自由扩散，降低了口服生物利用度。纳米颗粒给药可提高货物的生物利用度和细胞摄取率，并改善治疗效果，同时减少不必要的副作用。在这里，我们提出固体脂质纳米粒（SLNs）作为 LC 递送的疏水载体，旨在提高 LC 的生物利用度及其对细胞内氧化应激损伤的保护作用。LC-SLNs 是使用热匀化技术制备的，并研究了不同的理化性质。研究了普通 LC 和 LC-SLNs 对人脐静脉内皮细胞（HUVEC）中 HO 诱导的 ROS 生成的抑制作用。此外，还进行了各种体外实验，以评估 LC-SLNs 是否可以保护 HUVEC 免受 HO 诱导的遗传毒性和细胞凋亡。单分散和球形空白 SLNs 和 LC-SLNs 的粒径分别为 104±1.8 和 128±1.5nm，载药量（DL）分别为 11.49±0.78mg/mL 和可接受的包封效率（EE%）（69.09±1.12）的 LC-SLNs。制剂工艺不影响 LC 的抗氧化性能。MTT 法和彗星试验表明，LC-SLNs 降低了 HO 对 HUVEC 的细胞毒性和遗传毒性。此外，与普通 LC 相比，LC-SLNs 更能抑制 HO 处理的 HUVEC 中 ROS 的产生以及凋亡事件。总之，我们的研究结果证实了 LC-SLNs 对 HUVEC 中 HO 诱导的遗传毒性和细胞凋亡的保护作用。总之，LC-SLN 制剂是一种有前途的药物传递系统，可以克服亲水性 LC 的生物利用度问题，增强普通 LC 的抗氧化和生物学特性。
