Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000, Córdoba, Argentina.
Área de Cirugía de Vítreo y Retina, Centro Privado de Ojos Romagosa S.A. and Fundación VER, 5000, Córdoba, Argentina.
Exp Eye Res. 2020 Nov;200:108222. doi: 10.1016/j.exer.2020.108222. Epub 2020 Sep 6.
We are reporting for the first time the synthesis and application of an innovative nanometric system for the controlled topic release of melatonin in the retina. The ethylcellulose nanocapsules were characterized by diverse physicochemical techniques (scanning electron microscopy, zeta potential, hydrodynamic diameters) and an in vitro release study was done. A complete ex vivo and in vivo trans-corneal permeation and an irritation study were carried out with the new formulations in albino rabbits, to which a retinal degenerative model was induced. The results obtained demonstrate that the in vitro release of melatonin (1 mg/mL and 2 mg/mL) transported by nanocapsules is slower when compared to a solution of melatonin. Greater penetration of melatonin through the cornea was demonstrated by ex vivo and in vivo tests. This can be attributable to an enhanced neuroprotective effect of melatonin on retinal ganglion cells when it is included in ethylcellulose nanocapsules compared to a solution of melatonin. These outstanding findings add promising new perspectives to current knowledge about administrations using nano-technological tools in the treatment of neurodegenerative diseases at the ocular level.
我们首次报道了一种用于在视网膜中控制释放褪黑素的创新纳米系统的合成和应用。乙基纤维素纳米囊通过多种物理化学技术（扫描电子显微镜、Zeta 电位、水动力直径）进行了表征，并进行了体外释放研究。用新配方在诱导视网膜退行性病变的白化兔中进行了完整的体外和体内经角膜渗透和刺激性研究。结果表明，与褪黑素溶液相比，纳米囊输送的 1mg/mL 和 2mg/mL 褪黑素的体外释放更慢。通过离体和在体试验证明，褪黑素通过角膜的渗透能力更强。这可能归因于与褪黑素溶液相比，将褪黑素包含在乙基纤维素纳米囊内对视网膜神经节细胞具有增强的神经保护作用。这些卓越的发现为使用纳米技术工具在眼部治疗神经退行性疾病的现有知识增加了有前景的新视角。
