Department of Pharmaceutics and Drug Delivery, University of Mississippi, Mississippi, USA.
Department of Ophthalmology, The University of Tennessee Health Science Center, Hamilton Eye Institute, Memphis, Tennessee, USA.
J Ocul Pharmacol Ther. 2024 Oct;40(8):504-512. doi: 10.1089/jop.2024.0055. Epub 2024 Jul 8.
Fingolimod (FTY720; FT), a structural analog of sphingosine, has potential ocular applications. The goal of this study was to develop an FT-loaded nanoemulsion (NE; FT-NE) formulation for the efficient and prolonged delivery of FT to the posterior segment of the eye through the topical route. FT-NE formulations were prepared using homogenization followed by the probe sonication method. The lead FT-NE formulations (0.15% and 0.3% w/v loading), comprising soybean oil as oil and Tween 80 and Poloxamer 188 as surfactants, were further evaluated for release, surface morphology, filtration sterilization, and stability at refrigerated temperature. Ocular bioavailability following topical application of FT-NE (0.3%) was examined in Sprague-Dawley rats. The formulation, at both dose levels, showed desirable physicochemical characteristics, a nearly spherical shape with homogenous nanometric size distribution, and was stable for 180 days (last time point checked) at refrigerated temperature postfiltration through a polyethersulfone (0.22 µm) membrane. release studies showed prolonged release over 24 h, compared with the control FT solution (FT-S). studies revealed that effective concentrations of FT were achieved in the vitreous humor and retina following topical application of FT-NE. The results from these studies demonstrate that the FT-NE formulation can serve as a viable platform for the ocular delivery of FT through the topical route.
芬戈莫德（FTY720；FT）是一种鞘氨醇的结构类似物，具有潜在的眼部应用。本研究的目的是开发一种 FT 负载的纳米乳（NE；FT-NE）制剂，通过局部途径将 FT 高效且长时间递送至眼后段。使用均质化随后探针超声法制备 FT-NE 制剂。包含大豆油作为油相，吐温 80 和泊洛沙姆 188 作为表面活性剂的主导 FT-NE 制剂（0.15%和 0.3%w/v 负载量），进一步评估了释放、表面形态、过滤灭菌和冷藏温度下的稳定性。通过 Sprague-Dawley 大鼠研究了 FT-NE（0.3%）局部应用后的眼部生物利用度。在两种剂量水平下，制剂均表现出理想的理化特性，近乎球形，纳米级粒径分布均匀，在过滤通过聚醚砜（0.22 µm）膜后冷藏 180 天（最后检查时间点）稳定。释放研究表明，与对照 FT 溶液（FT-S）相比，FT-NE 可在 24 小时内延长释放。研究表明，局部应用 FT-NE 后可在玻璃体液和视网膜中达到有效的 FT 浓度。这些研究结果表明，FT-NE 制剂可作为通过局部途径递送至眼部的 FT 的可行平台。
