Structural modeling of drug release from biodegradable porous matrices based on a combined diffusion/erosion process
Structural modeling of drug release from biodegradable porous matrices based on a combined diffusion/erosion process
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DOI：
10.1016/s0378-5173(03)00165-0
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发表时间：
2003-06-04
影响因子：
5.8
通讯作者：
Hildgen, P
中科院分区：
文献类型：
--
作者：
Lemaire, V;Bélair, J;Hildgen, P
可生物降解的多孔微球表现出广泛的释放曲线。在本文中，我们提出了一个统一的方法，扩散和侵蚀的双重作用的基础上，建立哪些机制是负责在体外实验过程中观察到的各种释放动力学。我们的建模过程导致的矩阵分割成多个，相同的元素，从而大大简化了数学和数值处理的问题。模型方程不能解析求解，因为域包含移动界面，因此必须使用为此目的设计的特定方法进行数值求解。我们的模型证实了主要的作用，扩散和侵蚀之间的相对优势发挥释放动力学。特别是，侵蚀的速度，在润湿的聚合物中的药物分子的有效扩散系数，平均孔长度，和初始孔径是敏感的参数，而孔隙率和有效扩散系数的药物在溶剂填充的孔被认为是有很小的影响，如果有的话，对释放动力学。该模型是通过使用释放数据与不同比例的低和高分子量聚乳酸的生物可降解微球证实。通过改变所有类型的实验动力学的两个参数实现了极好的拟合优度：从典型的时间曲线的平方根到零级动力学到凹形释放曲线。我们也能够预测，通过插值，释放曲线从微球制成的中间，未经测试的比例的PLA通过使用两个模型参数之间的关系。(C)2003 Elsevier Science B.V.保留所有权利。
Biodegradable, porous microspheres exhibit a wide range of release profiles. We propose in this paper a unifying approach based on the dual action of diffusion and erosion to establish which mechanisms are responsible for the variety of release kinetics observed during in vitro experiments. Our modeling procedure leads to the partitioning of the matrix into multiple, identical elements, thus simplifying significantly the mathematical and numerical treatment of the problem. The model equations cannot be solved analytically, since the domain contains a moving interface, and must therefore be solved numerically, using specific methods designed for that purpose. Our model confirms the major role that the relative dominance between diffusion and erosion plays in the release kinetics. In particular, the velocity of erosion, the effective diffusion coefficient of the drug molecule in the wetted polymer, the average pore length, and the initial pore diameter are sensitive parameters, whereas the porosity and the effective diffusion coefficient of the drug in the solvent-filled pores is seen to have little influence, if any, on the release kinetics. The model is confirmed by using release data from biodegradable microspheres with different ratios of low and high molecular weight PLA. Excellent goodness of fit is achieved by varying two parameters for all types of experimental kinetics: from the typical square root of time profile to zero-order kinetics to concave release curves. We are also able to predict, by interpolation, release curves from microspheres made of intermediate, untested ratios of PLA by using a relation between two model parameters. (C) 2003 Elsevier Science B.V. All rights reserved.