PhD in Biotechnology, Department of Biomedical and Biotechnological Sciences, University of Catania, Via Santa Sofia 97, 95123 Catania, Italy; Laboratory of Drug Delivery Technology, Department of Drug and Health Sciences, University of Catania, Via Valdisavoia 5, 95123 Catania, Italy; Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028, Barcelona, Spain; NANOMED, Research Centre for Nanomedicine and Pharmaceutical Nanotechnology, University of Catania.
Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028, Barcelona, Spain; Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028, Barcelona, Spain; Unit of Synthesis and Biomedical Applications of Peptides, IQAC-CSIC, 08034, Barcelona, Spain.
Int J Pharm. 2024 Jul 20;660:124300. doi: 10.1016/j.ijpharm.2024.124300. Epub 2024 Jun 6.
Uveal melanoma is one of the most common and aggressive intraocular malignancies, and, due to its great capability of metastasize, it constitutes the most incident intraocular tumor in adults. However, to date there is no effective treatment since achieving the inner ocular tissues still constitutes one of the greatest challenges in actual medicine, because of the complex structure and barriers. Uncoated and PEGylated nanostructured lipid carriers were developed to achieve physico-chemical properties (mean particle size, homogeneity, zeta potential, pH and osmolality) compatible for the ophthalmic administration of (S)-(-)-MRJF22, a new custom-synthetized prodrug for the potential treatment of uveal melanoma. The colloidal physical stability was investigated at different temperatures by Turbiscan® Ageing Station. Morphology analysis and mucoadhesive studies highlighted the presence of small particles suitable to be topically administered on the ocular surface. In vitro release studies performed using Franz diffusion cells demonstrated that the systems were able to provide a slow and prolonged prodrug release. In vitro cytotoxicity test on Human Corneal Epithelium and Human Uveal Melanoma cell lines and Hen's egg-chorioallantoic membrane test showed a dose-dependent cytotoxic effect of the free prodrug on corneal cells, whose cytocompatibility improved when encapsulated into nanoparticles, as also confirmed by in vivo studies on New Zealand albino rabbits. Antiangiogenic capability and preventive anti-inflammatory properties were also investigated on embryonated eggs and rabbits, respectively. Furthermore, preliminary in vivo biodistribution images of fluorescent nanoparticles after topical instillation in rabbits' eyes, suggested their ability to reach the posterior segment of the eye, as a promising strategy for the treatment of choroidal uveal melanoma.
葡萄膜黑色素瘤是最常见和最具侵袭性的眼内恶性肿瘤之一，由于其强大的转移能力，它构成了成年人中最常见的眼内肿瘤。然而，迄今为止，由于要到达眼内组织仍然是实际医学中的最大挑战之一，因为其结构复杂且存在屏障，因此还没有有效的治疗方法。未涂层和 PEG 化的纳米结构化脂质载体被开发出来，以实现物理化学性质（平均粒径、均匀性、zeta 电位、pH 值和渗透压）与眼科给药（S）-（-）-MRJF22 兼容，（S）-（-）-MRJF22 是一种新合成的前药，用于潜在治疗葡萄膜黑色素瘤。通过 Turbiscan® 老化站在不同温度下研究胶体物理稳定性。形态分析和黏膜黏附研究突出了存在适合局部施用于眼表面的小颗粒。使用 Franz 扩散细胞进行的体外释放研究表明，这些系统能够提供缓慢且持续的前药释放。对人角膜上皮细胞和人葡萄膜黑色素瘤细胞系进行体外细胞毒性试验以及鸡胚绒毛尿囊膜试验表明，游离前药对角膜细胞具有剂量依赖性的细胞毒性作用，当将其包封在纳米颗粒中时，其细胞相容性得到改善，这也得到了新西兰白化兔体内研究的证实。还分别在鸡胚和兔子上研究了抗血管生成能力和预防性抗炎特性。此外，经眼部局部滴注后荧光纳米粒子的初步体内生物分布图像表明，它们能够到达眼睛的后段，这是治疗脉络膜葡萄膜黑色素瘤的有前途的策略。
