论文标题
来自具有可调网络特征的热响应水凝胶的夹杂纳米颗粒的受控释放
Controlled release of entrapped nanoparticles from thermoresponsive hydrogels with tunable network characteristics
论文作者
论文摘要
对热响应水凝胶进行了深入研究,以创建智能药物携带者和受控药物输送。了解热响应水凝胶网络中纳米颗粒(NP)的药物释放动力学和相应的传输机制是成功设计智能药物输送系统的关键。我们构建了一个固定NP的介质模型,该模型被夹在水凝胶网络中的水溶液中,其中水凝胶网络是由PNIPAM的交联半辅助聚合物形成的。通过改变PNIPAM较低临界溶液温度的环境温度,我们可以显着改变水凝胶网络特征。我们系统地研究了基质孔隙率和纳米颗粒的大小如何在不同温度下影响NPS的传输动力学。 NPS的均值位移和Van Hove位移分布的定量结果表明,夹在智能水凝胶中的所有NP都在低温和高温下都均受到细胞的次扩散。对于线圈状态,由于动能的增加和NP上的限制减少,副延伸指数和NP的扩散系数增加,而水凝胶中NP的运输也可以通过降低基质孔隙率和NPS的大小来增强。但是,当溶液温度升高到临界温度以上时,水凝胶网络在线圈到全球过渡后倒塌,NP紧紧地捕获在水凝胶内部的某些局部区域中。因此,可以通过两个数量级降低NP扩散系数,或者甚至可以完全停止扩散过程。这些发现为设计刺激性反应性水凝胶的受控药物释放提供了新的见解,包括自主打开/关闭药物释放以应对当地环境的变化。
Thermoresponsive hydrogels have been studied intensively for creating smart drug carriers and controlled drug delivery. Understanding the drug release kinetics and corresponding transport mechanisms of nanoparticles (NPs) in a thermoresponsive hydrogel network is the key to the successful design of a smart drug delivery system. We construct a mesoscopic model of rigid NPs entrapped in a hydrogel network in an aqueous solution, where the hydrogel network is formed by cross-linked semiflexible polymers of PNIPAM. By varying the environmental temperature crossing the lower critical solution temperature of PNIPAM we can significantly change the hydrogel network characteristics. We systematically investigate how the matrix porosity and the nanoparticle size affect the NPs' transport kinetics at different temperatures. Quantitative results on the mean-squared displacement and the van Hove displacement distributions of NPs show that all NPs entrapped in the smart hydrogels undergo subdiffusion at both low and high temperatures. For a coil state, the subdiffusive exponent and the diffusion coefficient of NPs increase due to the increased kinetic energy and the decreased confinement on NPs, while the transport of NPs in the hydrogels can be also enhanced by decreasing the matrix porosity and NPs' size. However, when the solution temperature is increased above the critical temperature, the hydrogel network collapses following the coil-to-globule transition, with the NPs tightly trapped in some local regions inside the hydrogels. Consequently, the NP diffusion coefficient can be reduced by two orders of magnitude, or the diffusion processes can even be completely stopped. These findings provide new insights for designing controlled drug release from stimuli-responsive hydrogels, including autonomously switch on/off drug release to respond to the changes of the local environment.