Diffusive Transport in the Vitreous Humor: Experimental and Analytical Studies.
Diffusive Transport in the Vitreous Humor: Experimental and Analytical Studies.
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玻璃体液中的扩散传输：实验和分析研究。
DOI：
10.1115/1.4042297
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Sadhal,SatwindarSingh
中科院分区：
文献类型：
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作者：
Penkova,Anita;Moats,Rex;Humayun,MarkS;Fraser,Scott;Sadhal,SatwindarSingh
关于玻璃体内药物递送，正在开发用于药物转运的预测数学模型，并且为了有效地实施这些用于视网膜递送，关于各种眼组织的生物物理性质的信息是根本重要的。因此，有必要准确测量药物和药物替代物在玻璃体液中的扩散系数。在这篇综述中，我们介绍了过去几十年来各种研究人员对这种测量进行的研究。这些包括成像技术（荧光和磁共振成像（MRI）），其利用将造影剂或标记药物引入玻璃体中并在不同时间点跟踪其扩散运动。当与实验测量值匹配时，相同初始条件的预测模型提供了扩散系数，导致大小范围为约0.1至160 kDa的各种分子的结果。对于真实的药物，该系统的有效性取决于用合适的造影剂如荧光素和钆或锰成功标记药物，从而可以进行荧光或MR成像。除了这种技术之外，已经进行了一些工作，使用扩散装置，通过在不同的时间间隔从腔室取样测定来测量药物穿过切除的玻璃体从供体腔室到受体的渗透。这具有不需要标记的优点，但在其他方面对玻璃体更具破坏性。使用动态光散射（DLS）已经实现了纳米颗粒的一些成功，并且目前正在探索放射性标记。
In relation to intravitreal drug delivery, predictive mathematical models for drug transport are being developed, and to effectively implement these for retinal delivery, the information on biophysical properties of various ocular tissues is fundamentally important. It is therefore necessary to accurately measure the diffusion coefficient of drugs and drug surrogates in the vitreous humor. In this review, we present the studies conducted by various researchers on such measurements over the last several decades. These include imaging techniques (fluorescence and magnetic resonance imaging (MRI)) that make use of introducing a contrast agent or a labeled drug into the vitreous and tracking its diffusive movement at various time points. A predictive model for the same initial conditions when matched with the experimental measurements provides the diffusion coefficient, leading to results for various molecules ranging in size from approximately 0.1 to 160 kDa. For real drugs, the effectiveness of this system depends on the successful labeling of the drugs with suitable contrast agents such as fluorescein and gadolinium or manganese so that fluorescence or MR imagining could be conducted. Besides this technique, some work has been carried out using the diffusion apparatus for measuring permeation of a drug across an excised vitreous body from a donor chamber to the receptor by sampling assays from the chambers at various time intervals. This has the advantage of not requiring labeling but is otherwise more disruptive to the vitreous. Some success with nanoparticles has been achieved using dynamic light scattering (DLS), and presently, radioactive labeling is being explored.