论文标题
使用增强的采样方法从粘土中释放药物的动力学
Kinetics of drug release from clay using enhanced sampling methods
论文作者
论文摘要
开发新药的关键步骤是设计导致最佳药物释放动力学的药物优异配合物的设计。计算化学，专门增强了采样分子动力学方法，可以通过最大程度地减少对昂贵的实验的需求并减少成本和时间来发挥关键作用。在这里，我们表明，在这一领域可以实现增强抽样方法的最新进展。我们通过模拟了水中复杂的质子 - 蒙山矿的释放动力学来证明这些方法的潜力。 Praziquantel在治疗血吸虫病时发现了有希望的应用，但是需要改进其生物制药剖面，像Montmorillonite粘土这样便宜的材料将是一种非常方便的赋形剂。我们模拟了从表面和层间空间释放的药物释放，发现药物从中间层间空间到溶液所花费的时间控制了释放时间。
A key step in the development of a new drug is the design of drug-excipient complexes that lead to an optimal drug release kinetics. Computational chemistry, specifically enhanced sampling molecular dynamics methods, can play a key role in this context by minimizing the need for expensive experiments and reducing cost and time. Here, we show that recent advances in enhanced sampling methodologies can be brought to fruition in this area. We demonstrate the potential of these methodologies by simulating the release kinetics of the complex praziquantel-montmorillonite in water. Praziquantel finds promising applications in the treatment of schistosomiasis, but its biopharmaceutical profile needs to be improved and a cheap material like the montmorillonite clay would be a very convenient excipient. We simulate the drug release both from surface and interlayer space and find that the time it takes to the drug to diffuse from the interlayer space to the solution controls the release time.
