Analytical and Computational Modeling of Sustained-Release Drug Implants in the Vitreous Humor.
Analytical and Computational Modeling of Sustained-Release Drug Implants in the Vitreous Humor.
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玻璃体液中缓释药物植入物的分析和计算模型。
DOI：
10.1115/1.4051785
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Sadhal,SatwindarSingh
中科院分区：
文献类型：
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作者：
Khoobyar,Anahid;Naghdloo,Amin;Penkova,AnitaN;Humayun,MarkS;Sadhal,SatwindarSingh
对于需要定期药物治疗的患者来说，持续的眼部药物输送系统是必要的，因为频繁注射是痛苦的、不良的且有风险的。一种类型的缓释系统包括负载药物的小丸，封装在可注射到玻璃体液中的多孔外壳中。释放的药物在那里扩散，而水的生理流动提供对流运输。玻璃体内的流体流动由用于分析模型的达西方程和用于计算分析的布林克曼流动来描述，而药物传输由经典的对流扩散方程给出。由于药物消耗的时间尺度相当大，对于分析模型，我们认为胶囊周围的外部是准稳态的，而内部是时间相关的。在玻璃体中，流体流动过程相对缓慢，并且对于小佩克莱特数可以获得有意义的结果，从而可以进行扰动分析。对于孤立的胶囊，在其周围的远场中具有近似均匀的流动，传质问题需要具有内部和外部匹配的奇异扰动。该计算模型除了适应目镜几何形状外，还允许完全依赖于时间的质量浓度解，并且还允许适度的佩克莱特数。正如预期的那样，由于药物耗尽降低了驱动潜力，释放速率随着时间的推移而降低。预测结果对于一定范围的胶囊渗透性值来说是足够普遍的，并且可用于根据特定药物所需的渗透性设计缓释微球。
Sustained ocular drug delivery systems are necessary for patients needing regular drug therapy since frequent injection is painful, undesirable, and risky. One type of sustained-release systems includes pellets loaded with the drug, encapsulated in a porous shell that can be injected into the vitreous humor. There the released drug diffuses while the physiological flow of water provides the convective transport. The fluid flow within the vitreous is described by Darcy's equations for the analytical model and Brinkman flow for the computational analysis while the drug transport is given by the classical convection–diffusion equation. Since the timescale for the drug depletion is quite large, for the analytical model, we consider the exterior surrounding the capsule to be quasi-steady and the interior is time dependent. In the vitreous, the fluid-flow process is relatively slow, and meaningful results can be obtained for small Peclet number whereby a perturbation analysis is possible. For an isolated capsule, with approximately uniform flow in the far field around it, the mass-transfer problem requires singular perturbation with inner and outer matching. The computational model, besides accommodating the ocular geometry, allows for a fully time-dependent mass-concentration solution and also admits moderate Peclet numbers. As expected, the release rate diminishes with time as the drug depletion lowers the driving potential. The predictive results are sufficient general for a range of capsule permeability values and are useful for the design of the sustained-release microspheres as to the requisite permeability for specific drugs.