NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain.
NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain; Histology and Cell Biology Department, Faculty of Medicine, University of Alexandria, Alexandria, Egypt.
Int J Pharm. 2018 Dec 1;552(1-2):48-55. doi: 10.1016/j.ijpharm.2018.09.038. Epub 2018 Sep 19.
Development of safe and efficient non-viral vectors to deliver DNA into the CNS represents a huge challenge to face many neurological disorders. We elaborated niosomes based on DOTMA cationic lipid, lycopene "helper" lipid and polysorbate 60 as non-ionic surfactants for gene delivery to the CNS. Niosomes, and their corresponding nioplexes obtained after the addition of the pCMS-EGFP plasmid, were characterized in terms of size, charge, morphology and capacity to condense, release and protect DNA. In vitro experiments were performed in NT2 cells to evaluate transfection efficiency, viability, cellular uptake and intracellular distribution. Additionally, transfection in primary cortex cells were performed prior to brain administration into rat cerebral cortex. Data obtained showed that nioplexes exhibited not only adequate physicochemical properties for gene delivery applications, but also relevant transfection efficiencies (17%), without hampering viability (90%). Interestingly, In vivo experiments depicted promising protein expression in both cortical glial cells and blood vessels.
开发安全有效的非病毒载体将 DNA 递送至中枢神经系统是应对许多神经疾病的巨大挑战。我们基于 DOTMA 阳离子脂质、番茄红素“辅助”脂质和聚山梨醇酯 60 来研制了用于向中枢神经系统递基因的脂囊泡。我们对脂囊泡及其在加入 pCMS-EGFP 质粒后获得的相应脂复合物的大小、电荷、形态和缩合、释放和保护 DNA 的能力进行了表征。我们在 NT2 细胞中进行了体外实验，以评估转染效率、细胞活力、细胞摄取和细胞内分布。此外，在将复合物递送至大鼠大脑皮层之前，我们在原代皮质细胞中进行了转染。获得的数据表明，脂复合物不仅具有适用于基因递释应用的足够理化性质，而且还具有相关的转染效率（17%），而不会损害细胞活力（90%）。有趣的是，体内实验显示出在皮质神经胶质细胞和血管中都有有前景的蛋白表达。
