Khoobyar Anahid, Naghdloo Amin, Penkova Anita N, Humayun Mark S, Sadhal Satwindar Singh
Department of Aerospace & Mechanical Engineering, University of Southern California, USC Viterbi School of Engineering, Los Angeles, CA 90089-1453.
Department of Aerospace & Mechanical Engineering, University of Southern California, USC Viterbi School of Engineering, Los Angeles, CA 90089-1453; Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA 90027.
J Heat Transfer. 2021 Oct 1;143(10):101201. doi: 10.1115/1.4051785. Epub 2021 Sep 8.
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.
对于需要长期药物治疗的患者来说，持续眼部给药系统是必要的，因为频繁注射既痛苦又不理想，还存在风险。一种缓释系统包括装载药物的微丸，微丸被封装在一个多孔壳中，可注射到玻璃体内。在那里，释放的药物扩散，而水的生理流动提供对流传输。玻璃体内的流体流动在分析模型中用达西方程描述，在计算分析中用布林克曼流描述，而药物传输由经典的对流扩散方程给出。由于药物耗尽的时间尺度相当大，对于分析模型，我们认为胶囊外部环境是准稳态的，而内部是随时间变化的。在玻璃体内，流体流动过程相对较慢，对于小佩克莱数可以得到有意义的结果，从而可以进行微扰分析。对于一个孤立的胶囊，其周围远场流动近似均匀，传质问题需要内外部匹配的奇异微扰。计算模型除了考虑眼部几何形状外，还允许完全随时间变化的质量浓度解，并且也允许中等佩克莱数。正如预期的那样，随着药物耗尽降低驱动势，释放速率随时间降低。预测结果对于一系列胶囊渗透率值具有足够的通用性，对于设计特定药物所需渗透率的缓释微球很有用。
