Sevim Kevser, Pan Jingzhe
Department of Engineering, University of Leicester , Leicester LE1 7RH, U.K.
Mol Pharm. 2016 Aug 1;13(8):2729-35. doi: 10.1021/acs.molpharmaceut.6b00313. Epub 2016 Jul 19.
Polyester microspheres are extensively studied for controlled release drug delivery devices, and many models have been developed to describe drug release from the bulk polymer. However, the interaction between drugs and polymers is ignored in most of the existing mathematical models. This paper presents a mechanistic model which captures the interplay between acidic drugs and bioresorbable polyesters. The model considers the autocatalytic effect on polymer degradation arising from carboxylic acid end groups of oligomers and drug molecules. Hence, the enhancing effect of acidic drug on the rate of degradation was fully considered. On the other hand the drug release from polyester microspheres is controlled by drug diffusion from polymer matrix. The drug diffusion coefficient depends strongly on the level of degradation of the polymer. This effect is also included in the model. It is shown that the model can effectively predict experimental data in the literature for both polymer degradation and drug release. Furthermore, the model is used to design different systems of microspheres which release drugs with either a zero order profile or burst followed by zero order release profile.
聚酯微球在控释给药装置方面得到了广泛研究，并且已经开发了许多模型来描述药物从块状聚合物中的释放。然而，在大多数现有的数学模型中，药物与聚合物之间的相互作用被忽略了。本文提出了一个机理模型，该模型捕捉了酸性药物与可生物降解聚酯之间的相互作用。该模型考虑了低聚物和药物分子的羧酸端基对聚合物降解产生的自催化作用。因此，充分考虑了酸性药物对降解速率的增强作用。另一方面，聚酯微球中的药物释放受药物从聚合物基质中的扩散控制。药物扩散系数强烈依赖于聚合物的降解程度。这种效应也包含在模型中。结果表明，该模型能够有效地预测文献中关于聚合物降解和药物释放的实验数据。此外，该模型用于设计不同的微球系统，这些系统可以以零级模式释放药物，或者先有一个突释然后再以零级释放模式释放药物。
