论文标题
基于水凝胶的药物递送系统的最佳负载
Optimal loading of hydrogel-based drug-delivery systems
论文作者
论文摘要
加载的水凝胶提供了一种以受控速率将药物剂传递到体内特定部位的方法。本文的目的是了解如何通过调整水凝胶中药物分子的初始分布来实现受控药物释放。为球形药物的水凝胶提供了数学模型。该模型捕获了聚合物网络的非线性弹性和肿胀的热力学。通过假设药物分子是稀释的，水凝胶肿胀和药物转运的方程会部分脱离。开发了一种快速优化方法，以通过最大程度地减少数值药物释放曲线和目标剖面之间的误差来准确计算最佳初始药物浓度。通过将目标药物外排为分段常数，最佳初始构型由中央药物的核心组成，并在水凝胶的自由边界附近，其孤立的药品包组成。最佳的初始药物浓度在缓解爆发效果方面非常有效，其中大量药物被迅速释放到环境中。水凝胶刚度可用于进一步调整药物释放速率。尽管更硬的凝胶会导致肿胀较少，因此降低了药物的扩散率，但由于药物分子必须传播以达到自由表面的距离，药物释放动力学的速度比软凝胶要快。
Drug-loaded hydrogels provide a means to deliver pharmaceutical agents to specific sites within the body at a controlled rate. The aim of this paper is to understand how controlled drug release can be achieved by tuning the initial distribution of drug molecules in a hydrogel. A mathematical model is presented for a spherical drug-loaded hydrogel. The model captures the nonlinear elasticity of the polymer network and thermodynamics of swelling. By assuming that the drug molecules are dilute, the equations for hydrogel swelling and drug transport partially decouple. A fast optimisation method is developed to accurately compute the optimal initial drug concentration by minimising the error between the numerical drug-release profile and a target profile. By taking the target drug efflux to be piecewise constant, the optimal initial configuration consists of a central drug-loaded core with isolated drug packets near the free boundary of the hydrogel. The optimal initial drug concentration is highly effective at mitigating the burst effect, where a large amount of drug is rapidly released into the environment. The hydrogel stiffness can be used to further tune the rate of drug release. Although stiffer gels lead to less swelling and hence reduce the drug diffusivity, the drug-release kinetics are faster than for soft gels due to the decreased distance that drug molecules must travel to reach the free surface.
