Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche, Università Politecnica delle Marche, Via Brecce Bianche, 60131 Ancona, Italy.
Int J Pharm. 2013 Oct 15;455(1-2):348-56. doi: 10.1016/j.ijpharm.2013.06.075. Epub 2013 Jul 9.
Nanostructured lipid carriers (NLC) represent an emerging tool for drug delivery and are characterized by important features which promote increased bioavailability and epithelial penetration of lipophilic compounds. However, despite these advantages, their potential cytotoxicity should not be underestimated, especially under in vivo usage conditions. Here we analyzed the viability, intracellular reactive oxygen species (ROS), oxidative DNA damage and mitochondrial functionality in human dermal fibroblasts (HDF) in the presence of NLC either empty or loaded with the reduced or oxidized form of Coenzyme Q10. Experiments were carried out under standard culture conditions and under oxidative stress induced by UVA irradiation, where the latter treatment significantly affected all the endpoints tested above compared to the non-UVA condition. The data show that NLC alone, whether exposed or not exposed to UVA, produce a slight, though significant decrease in cell viability associated with enhanced oxidative stress, which did not however lead to oxidative DNA damage nor mitochondrial impairment. Reduced CoQ10-NLC, differently from oxidized CoQ10-NLC, were able to efficiently counteract UVA-associated mitochondrial depolarization suggesting a potential role of this molecule in antiageing cosmetological formulations. In conclusion, our results suggest that interactions of NLC with cells and biomolecules should be routinely assessed for understanding their compatibility and toxicity, not only under normal conditions, but also under any chemical or physical stress which these delivery systems might be subjected to during their employment.
纳米结构脂质载体 (NLC) 是一种用于药物传递的新兴工具,具有促进亲脂性化合物生物利用度和上皮穿透性的重要特性。然而,尽管有这些优势,其潜在的细胞毒性不应被低估,特别是在体内使用条件下。在这里,我们分析了人真皮成纤维细胞 (HDF) 在存在空的或负载还原或氧化形式辅酶 Q10 的 NLC 时的活力、细胞内活性氧 (ROS)、氧化 DNA 损伤和线粒体功能。实验在标准培养条件下和 UVA 照射诱导的氧化应激下进行,与非 UVA 条件相比,后者处理显著影响了上述所有测试终点。数据表明,NLC 本身,无论是否暴露于 UVA 下,都会导致细胞活力轻微但显著下降,同时伴随着氧化应激增强,但这并不会导致氧化 DNA 损伤或线粒体损伤。与氧化 CoQ10-NLC 不同,还原 CoQ10-NLC 能够有效地对抗 UVA 相关的线粒体去极化,表明该分子在抗衰老化妆品配方中可能具有潜在作用。总之,我们的结果表明,应常规评估 NLC 与细胞和生物分子的相互作用,以了解其相容性和毒性,不仅在正常条件下,而且在这些输送系统在使用过程中可能受到的任何化学或物理应激下也是如此。