Kalosakas George
Materials Science Department, University of Patras, GR-26504 Rio, Greece.
Materials (Basel). 2023 Jun 26;16(13):4595. doi: 10.3390/ma16134595.
In conjugated polymeric drug delivery systems, both the covalent bond degradation rate and the diffusion of the freely moving drug particles affect the release profile of the formulation. Using Monte Carlo simulations in spherical matrices, the release kinetics resulting from the competition between the reaction and diffusion processes is discussed. For different values of the relative bond cleavage rate, varied over four orders of magnitude, the evolution of (i) the number of bonded drug molecules, (ii) the fraction of the freely moved detached drug within the polymer matrix, and (iii) the resulting fractional release of the drug is presented. The characteristic release time scale is found to increase by several orders of magnitude as the cleavage reaction rate constant decreases. The two extreme rate-limiting cases where either the diffusion or the reaction dominates the release are clearly distinguishable. The crossover between the diffusion-controlled and reaction-controlled regimes is also examined and a simple analytical formula is presented that can describe the full dependence of the release time on the bond cleavage rate constant. This simple relation is provided simply by the sum of the characteristic time for purely diffusional release and the bond cleavage decay time, which equals the inverse of the reaction rate constant.
在共轭聚合物药物递送系统中，共价键降解速率和自由移动的药物颗粒扩散都会影响制剂的释放曲线。利用球形基质中的蒙特卡罗模拟，讨论了反应和扩散过程之间竞争导致的释放动力学。对于相对键断裂速率在四个数量级范围内变化的不同值，给出了（i）键合药物分子数量、（ii）聚合物基质内自由移动的解离药物分数以及（iii）由此产生的药物分数释放的演变情况。发现随着裂解反应速率常数的降低，特征释放时间尺度增加了几个数量级。扩散或反应主导释放的两种极端速率限制情况清晰可辨。还研究了扩散控制和反应控制区域之间的交叉，并给出了一个简单的解析公式，该公式可以描述释放时间对键断裂速率常数的完全依赖性。这个简单关系仅由纯扩散释放的特征时间与键断裂衰减时间之和给出，该和等于反应速率常数的倒数。
