Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, 5000 Córdoba, Argentina.
Área de Cirugía de Vítreo y Retina, Centro Privado de Ojos Romagosa S.A. and Fundación VER, 5000 Córdoba, Argentina.
Int J Pharm. 2022 Nov 25;628:122308. doi: 10.1016/j.ijpharm.2022.122308. Epub 2022 Oct 17.
The use of proteins such as human serum albumin (HSA) to form nanometric systems seems very promising since they are non-toxic, biodegradable and have no antigenic activity. This molecule is ideal to transport insoluble drugs such as melatonin (Mel), which has antiapoptotic and antioxidant properties and appears promising for the treatment of neurodegenerative eye diseases. The objective of this study was to obtain nanoparticulate systems loaded with Mel, improving the conventional desolvation method. Systems were stabilised using two different strategies: one through the use of Eudragit S100 as a cross-linking agent and the other through thermal stabilisation. The systems thus obtained (Np-HSA-Eu-Mel and Np-HSA-Mel, respectively) were characterised and compared in terms of physicochemical and pharmacotechnical parameters. Whitish colloidal dispersions of nanometric size (≈170 nm), spherical shape, and monodisperse population were obtained. Besides, the pH was close to neutrality reaching 20 % drug encapsulation whereas the process performance was higher than 80 %. In FT-IR studies, thermal analysis and X-ray diffraction (XRD), the incorporation of the drug in the cavities of the nanoparticles could be evidenced. Regarding the physical stability of nanoparticles, for Np-HSA-Eu-Mel instability was observed at pH > 7. However, Np-HSA-Mel was able to remain stable at different pH levels. Mel release from these systems was consequently affected, where the former released faster than the active compared to the last. On the other hand, it was observed that the drying process (lyophilization in this case) applied to the nanoparticles suspensions does not affect their original properties after redispersion over a three months period. Likewise, the formulation did not produce irritation when administered topically, whereas when administered subconjunctivally, only slight irritation was observed 24 h after administration. According to the result of this study, the Np-HSA-Mel formulation could achieve advantageous properties as a vehicle for the transport of insoluble drugs for the treatment of neurodegenerative diseases at the ocular level.
使用人血清白蛋白（HSA）等蛋白质形成纳米系统似乎非常有前景，因为它们无毒、可生物降解且没有抗原活性。这种分子是运输不溶性药物（如 melatonin，具有抗细胞凋亡和抗氧化特性，有望用于治疗神经退行性眼病）的理想选择。本研究的目的是获得负载 melatonin 的纳米颗粒系统，改进常规的去溶剂化方法。通过使用 Eudragit S100 作为交联剂和通过热稳定化来稳定系统。分别获得了得到的系统（Np-HSA-Eu-Mel 和 Np-HSA-Mel），并在物理化学和药剂学参数方面进行了比较。得到了粒径约为 170nm、球形、单分散的白色胶体分散体。此外，pH 值接近中性，达到 20%的药物包封率，而工艺性能高于 80%。在 FT-IR 研究、热分析和 X 射线衍射（XRD）中，可以证明药物被包封在纳米颗粒的空腔中。关于纳米颗粒的物理稳定性，对于 Np-HSA-Eu-Mel，在 pH>7 时观察到不稳定性。然而，Np-HSA-Mel 能够在不同的 pH 水平下保持稳定。因此，这些系统中 melatonin 的释放受到影响，其中前者的释放速度比后者快。另一方面，观察到对纳米颗粒悬浮液进行的干燥过程（在此情况下为冻干）在重新分散三个月后不会影响其原始性质。同样，该制剂在局部给药时不会引起刺激，而在结膜下给药时，给药后 24 小时仅观察到轻微刺激。根据这项研究的结果，Np-HSA-Mel 制剂可以作为一种载体，用于运输不溶性药物，以治疗眼部的神经退行性疾病。
