Davies Alys E, Williams Rachel L, Lugano Gaia, Pop Serban R, Kearns Victoria R
Department of Eye and Vision Science, University of Liverpool, Liverpool, UK.
Department of Computer Science, University of Chester, Chester, UK.
Interface Focus. 2020 Apr 6;10(2):20190132. doi: 10.1098/rsfs.2019.0132. Epub 2020 Feb 14.
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 and 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 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 results. This model could be used as a predictive tool for drug transport across this important tissue.
生成快速、经济高效且与人体相关的数据的能力，有可能加速新型药物递送系统的开发。由于与年龄增长和生活方式因素相关的致盲疾病增多，眼内药物递送领域正在迅速扩张。外血视网膜屏障（OBRB）在该药物递送领域很重要，因为它将眼睛与全身血流分隔开。本研究报告了用于研究硅油中药物透过OBRB转运的互补模型的开发。将人视网膜色素上皮细胞系ARPE - 19的单层培养物添加到小室中，并使其暴露于可控流中，以模拟药物透过OBRB的清除过程。测量了该模型中葡聚糖分子的移动以及布洛芬从硅油中的释放情况。使用COMSOL Multiphysics计算流体动力学软件进行了相应模拟，并使用独立数据集进行了验证。计算模拟能够预测葡聚糖的移动和布洛芬的释放，模拟数据中观察到了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的峰值浓度模拟值与实验结果的偏差在18%以内。该模型可作为预测药物透过这一重要组织的转运情况的工具。
