Rothstein Sam N, Federspiel William J, Little Steven R
Department of Chemical Engineering, University of Pittsburgh, 3501 Fifth Avenue, Pittsburgh, PA 15203, USA.
Biomaterials. 2009 Mar;30(8):1657-64. doi: 10.1016/j.biomaterials.2008.12.002. Epub 2008 Dec 19.
A unified model has been developed to predict release not only from bulk eroding and surface eroding systems but also from matrices that transition from surface eroding to bulk eroding behavior during the course of degradation. This broad applicability is afforded by fundamental diffusion/reaction equations that can describe a wide variety of scenarios including hydration of and mass loss from a hydrolysable polymer matrix. Together, these equations naturally account for spatial distributions of polymer degradation rate. In this model paradigm, the theoretical minimal size required for a matrix to exhibit degradation under surface eroding conditions was calculated for various polymer types and then verified by empirical data from the literature. An additional set of equations accounts for dissolution- and/or degradation-based release, which are dependent upon hydration of the matrix and erosion of the polymer. To test the model's accuracy, predictions for agent egress were compared to experimental data from polyanhydride and polyorthoester implants that were postulated to undergo either dissolution-limited or degradation-controlled release. Because these predictions are calculated solely from readily attainable design parameters, it seems likely that this model could be used to guide the design controlled release formulations that produce a broad array of custom release profiles.
已经开发出一种统一模型，不仅可以预测从整体侵蚀和表面侵蚀系统的释放，还可以预测在降解过程中从表面侵蚀转变为整体侵蚀行为的基质的释放。这种广泛的适用性由基本的扩散/反应方程提供，这些方程可以描述包括可水解聚合物基质的水合作用和质量损失在内的各种情况。这些方程共同自然地说明了聚合物降解速率的空间分布。在这个模型范式中，针对各种聚合物类型计算了基质在表面侵蚀条件下表现出降解所需的理论最小尺寸，然后通过文献中的经验数据进行了验证。另一组方程考虑了基于溶解和/或降解的释放，这取决于基质的水合作用和聚合物的侵蚀。为了测试模型的准确性，将药物释放的预测结果与聚酸酐和聚原酸酯植入物的实验数据进行了比较，这些植入物被假定经历溶解限制或降解控制释放。由于这些预测仅根据易于获得的设计参数计算得出，因此该模型似乎可用于指导设计可控释放制剂，从而产生广泛的定制释放曲线。
