Implantable, bioresorbable drug delivery systems offer an alternative to current drug administration techniques; allowing for patient-tailored drug dosage, while also increasing patient compliance. Mechanistic mathematical modeling allows for the acceleration of the design of the release systems, and for prediction of physical anomalies that are not intuitive and may otherwise elude discovery. This study investigates short-term drug release as a function of water-mediated polymer phase inversion into a solid depot within hours to days, as well as long-term hydrolysis-mediated degradation and erosion of the implant over the next few weeks. Finite difference methods are used to model spatial and temporal changes in polymer phase inversion, solidification, and hydrolysis. Modeling reveals the impact of non-uniform drug distribution, production and transport of H⁺ ions, and localized polymer degradation on the diffusion of water, drug, and hydrolyzed polymer byproducts. Compared to experimental data, the computational model accurately predicts the drug release during the solidification of implants over days and drug release profiles over weeks from microspheres and implants. This work offers new insight into the impact of various parameters on drug release profiles, and is a new tool to accelerate the design process for release systems to meet a patient specific clinical need.

中文翻译：

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可植入、生物可吸收药物释放系统的机械计算模型

可植入、生物可吸收的药物输送系统提供了当前药物管理技术的替代方案；允许患者定制药物剂量，同时也提高患者的依从性。机械数学建模可以加速释放系统的设计，并预测不直观且可能无法发现的物理异常。这项研究调查了短期药物释放作为水介导的聚合物在数小时至数天内转变成固体储库的函数，以及在接下来的几周内植入物的长期水解介导的降解和侵蚀。有限差分方法用于模拟聚合物相转化、凝固和水解的空间和时间变化。建模揭示了不均匀的药物分布、H ⁺离子的产生和运输以及局部聚合物降解对水、药物和水解聚合物副产物扩散的影响。与实验数据相比，计算模型准确预测了植入物固化过程中数天内的药物释放情况以及数周内微球和植入物的药物释放曲线。这项工作提供了关于各种参数对药物释放曲线的影响的新见解，并且是加速释放系统设计过程以满足患者特定临床需求的新工具。