The ability to produce rapid, cost-effective and human-relevant data has the potential to accelerate the development of new drug delivery systems. Intraocular drug delivery is an area undergoing rapid expansion, due to the increase in sight-threatening diseases linked to increasing age and lifestyle factors. The outer blood-retinal barrier (OBRB) is important in this area of drug delivery, as it separates the eye from the systemic blood flow. This study reports the development of complementary in vitro and in silico models to study drug transport from silicone oil across the OBRB. Monolayer cultures of a human retinal pigmented epithelium cell line, ARPE-19, were added to chambers and exposed to a controlled flow to simulate drug clearance across the OBRB. Movement of dextran molecules and release of ibuprofen from silicone oil in this model were measured. Corresponding simulations were developed using COMSOL Multiphysics computational fluid dynamics software and validated using independent in vitro datasets. Computational simulations were able to predict dextran movement and ibuprofen release, with all of the features of the experimental release profiles being observed in the simulated data. Simulated values for peak concentrations of permeated dextran and ibuprofen released from silicone oil were within 18% of the in vitro results. This model could be used as a predictive tool for drug transport across this important tissue.

中文翻译：

---

穿过外血视网膜屏障的药物输送的体外和计算模型。


产生快速、具有成本效益且与人类相关的数据的能力有可能加速新药物输送系统的开发。由于与年龄增长和生活方式因素相关的威胁视力的疾病增加，眼内给药是一个正在快速扩张的领域。外血视网膜屏障 (OBRB) 在药物输送领域非常重要，因为它将眼睛与全身血流分开。本研究报告了互补的体外和计算机模型的开发，以研究药物从硅油穿过 OBRB 的转运。将人视网膜色素上皮细胞系 ARPE-19 的单层培养物添加到室中并暴露于受控流中以模拟通过 OBRB 的药物清除。测量了该模型中葡聚糖分子的运动和硅油中布洛芬的释放。使用 COMSOL Multiphysics 计算流体动力学软件开发了相应的模拟，并使用独立的体外数据集进行了验证。计算模拟能够预测右旋糖酐运动和布洛芬释放，并在模拟数据中观察到实验释放曲线的所有特征。从硅油中释放的渗透葡聚糖和布洛芬峰值浓度的模拟值与体外结果的误差在 18% 以内。该模型可以用作药物在这一重要组织中转运的预测工具。