Department of Chemistry, Zhejiang University, Hangzhou 310027, People's Republic of China.
Hangzhou Medical College, Hangzhou 310013, People's Republic of China.
Int J Pharm. 2020 Apr 30;580:119241. doi: 10.1016/j.ijpharm.2020.119241. Epub 2020 Mar 17.
Doxorubicin (DOX) is a broad-spectrum anti-tumor drug, but it has certain limitations in its therapeutic effects due to poor tumor selectivity. Chitosan-based pH-sensitive polymers drug delivery systems could improve DOX's activity and selectivity against tumor cells. Understanding the atomic interaction mechanism between chitosan and DOX at different pH levels is important in the design and application of chitosan-based drug delivery systems. In this study, molecular dynamics simulations were performed to investigate the encapsulation and release of DOX by chitosan at different pH levels. Our results show that the protonation state of amine groups of chitosan and the π-π stacking interaction between the conjugated anthraquinone ring of DOX regulate the interaction behavior between chitosan and DOX. Moreover, DOX could gradually release from chitosan at acidic pH environment in tumor tissue. These results revealed the underlying atomic interaction mechanism between DOX and chitosan at various pH levels and may provide novel ideas for the design and application of chitosan-based drug delivery system.
多柔比星（DOX）是一种广谱抗肿瘤药物，但由于其对肿瘤的选择性差，其治疗效果存在一定的局限性。基于壳聚糖的 pH 敏感聚合物药物传递系统可以提高 DOX 对肿瘤细胞的活性和选择性。了解壳聚糖与 DOX 在不同 pH 值下的原子相互作用机制，对于设计和应用基于壳聚糖的药物传递系统非常重要。在这项研究中，进行了分子动力学模拟，以研究不同 pH 值下壳聚糖对 DOX 的包封和释放。我们的结果表明，壳聚糖的氨基质子化状态和 DOX 的共轭蒽醌环之间的π-π堆积相互作用调节了壳聚糖与 DOX 之间的相互作用行为。此外，DOX 可以在肿瘤组织的酸性 pH 环境中逐渐释放。这些结果揭示了不同 pH 值下 DOX 与壳聚糖之间的原子相互作用机制，并可能为基于壳聚糖的药物传递系统的设计和应用提供新的思路。
