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A Mechanistic Model for Drug Release in PLGA Biodegradable Stent Coatings Coupled with Polymer Degradation and Erosion

机译:PLGA可生物降解支架涂料与聚合物降解和侵蚀相结合的药物释放机理模型。

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摘要

Biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA) coating for applications in drug-eluting stents has been receiving increasing interest as a result of its unique properties compared with biodurable polymers in delivering drug for reducing stents-related side effects. In this work, a mathematical model for describing the PLGA degradation and erosion and coupled drug release from PLGA stent coating is developed and validated. An analytical expression is derived for PLGA mass loss that predicts multiple experimental studies in the literature. An analytical model for the change of the number-average degree of polymerization (or molecular weight) is also derived. The drug transport model incorporates simultaneous drug diffusion through both the polymer solid and the liquid-filled pores in the coating, where an effective drug diffusivity model is derived taking into account factors including polymer molecular weight change, stent coating porosity change, and drug partitioning between solid and aqueous phases. The model is used to describe in vitro sirolimus release from PLGA stent coating, and demonstrates the significance of simultaneous sirolimus release via diffusion through both polymer solid and pore space. The proposed model is compared to existing drug transport models, and the impact of model parameters, limitations and possible extensions of the model are also discussed.
机译:与可生物降解的聚合物相比,可生物降解的聚(D,L-乳酸-乙醇酸共聚物)(PLGA)涂层在药物洗脱支架中的应用引起了越来越多的关注,因为它具有独特的性能,可用于减少支架相关侧面的药物输送效果。在这项工作中,开发并验证了用于描述PLGA降解和侵蚀以及PLGA支架涂层中耦合药物释放的数学模型。推导了PLGA质量损失的解析表达式,该表达式预测了文献中的多次实验研究。还推导了改变数均聚合度(或分子量)的分析模型。药物传输模型结合了同时通过涂层中的聚合物固体和液体填充孔进行的药物扩散,其中考虑了包括聚合物分子量变化,支架涂层孔隙率变化以及药物之间的分配等因素,得出了有效的药物扩散模型。固相和水相。该模型用于描述PLGA支架涂层从体外释放西罗莫司的情况,并证明了西罗莫司通过聚合物固体和孔空间扩散而同时释放的重要性。将提出的模型与现有的药物运输模型进行比较,并讨论了模型参数的影响,模型的局限性和可能的​​扩展。

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