Department of Chemical Sciences, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy.
Molecules. 2023 Jul 22;28(14):5581. doi: 10.3390/molecules28145581.
The development of novel drug delivery systems (DDSs) with promising antibacterial properties is essential for facing the emergency of increasing resistance to antimicrobial agents. The antibacterial features of quercetin and its metal complexes have been broadly investigated. However, several drawbacks affect their activity and effectiveness. In this work, we propose a DDS based on a pH-responsive cobalt(II)-coordinated assembly containing quercetin and polyacrylic acid. This system is suggested to trigger the release of the model drug in a pH-dependent mode by exploiting the localized acidic environment at the bacterial infection sites under anaerobic conditions. The delivery system has been designed by accurately examining the species and the multiple equilibria occurring in solution among the assembly components. The formation of cobalt(II) complexes with quercetin in the absence or presence of the pH-responsive polyacrylic acid was investigated in buffered aqueous solution at pH 7.4 using spectrophotometric (UV-Vis) and calorimetric (ITC) techniques. The determined binding affinities and thermodynamic parameters that resulted are essential for the development of a DDS with improved binding and release capabilities. Furthermore, the affinity of the polymer-cobalt(II) complex toward the model antimicrobial flavonoid was explored at the solid-liquid interface by quartz crystal microbalance (QCM-D) experiments, which provided marked evidence for drug loading and release under pH control.
新型药物传递系统（DDS）的开发具有有前景的抗菌性能，对于应对抗菌药物耐药性日益增加的紧急情况至关重要。槲皮素及其金属配合物的抗菌特性已得到广泛研究。然而，一些缺点影响了它们的活性和效果。在这项工作中，我们提出了一种基于 pH 响应的钴(II)配位组装的 DDS，其中包含槲皮素和聚丙烯酸。该系统通过利用厌氧条件下细菌感染部位局部酸性环境，建议以 pH 依赖的方式触发模型药物的释放。该传递系统是通过仔细检查组装成分在溶液中的物种和多种平衡来设计的。在 pH 7.4 的缓冲水溶液中，使用分光光度法（UV-Vis）和量热法（ITC）技术研究了在不存在或存在 pH 响应性聚丙烯酸的情况下，槲皮素与钴(II)的配合物的形成。确定的结合亲和力和热力学参数对于开发具有改善结合和释放能力的 DDS 至关重要。此外，通过石英晶体微天平（QCM-D）实验研究了聚合物-钴（II）配合物对模型抗菌类黄酮在固液界面的亲和力，这为 pH 控制下的药物负载和释放提供了明显的证据。
