POLYMAT, Applied Chemistry Department, Faculty of Chemistry, University of the Basque Country UPV/EHU, Paseo Manuel de Lardizabal 3, Donostia-San Sebastián 20018, Spain.
Biomedical Polymers Division, Research Institute for Materials Science and Technology (INTEMA), National University of Mar del Plata (UNMdP)-National Scientific and Technical Research Council (CONICET), Av. Colón 10850, Mar del Plata 7600, Argentina.
Biomacromolecules. 2024 Sep 9;25(9):5968-5978. doi: 10.1021/acs.biomac.4c00633. Epub 2024 Aug 27.
Effective drug delivery to bacterially infected mucosa remains a challenge due to the combined obstacles of the mucosal barrier, pH variations, and high concentrations of glutathione. However, polysaccharide-based responsive nanogels (NGs) can take advantage of these conditions to deliver specific antimicrobials. We explored the critical features of pH- and redox-responsive NGs to increase drug penetration, residence time, and efficacy in the infected mucosa. We prepared multifunctional NGs using hydroxypropyl cellulose as a template for the cross-linking of methacrylic acid with ,'-bis(acryloyl)cystamine (BAC) or ,'-methylenebis(acrylamide) (BIS). Studies of NG-mucin binding and the antibacterial efficacy of doxycycline-loaded NGs revealed the interplay between the response to pH and redox clues. Specifically, higher BAC composition increased mucus binding and controlled release in reductive conditions, while higher BIS composition yielded NGs with higher doxycycline-mediated antibacterial efficacy against . The findings reveal the potential of multiresponsive NGs in effective antimicrobial delivery in infected mucosa.
由于黏膜屏障、pH 值变化和高浓度谷胱甘肽的共同阻碍，将药物有效递送到细菌感染的黏膜仍然是一个挑战。然而，基于多糖的响应性纳米凝胶 (NG) 可以利用这些条件来输送特定的抗菌药物。我们探索了 pH 和氧化还原响应性 NGs 的关键特性，以增加药物在感染黏膜中的穿透性、滞留时间和疗效。我们使用羟丙基纤维素作为模板，通过甲基丙烯酸与双(丙烯酰基)胱氨酸 (BAC) 或,'-亚甲基双(丙烯酰胺) (BIS) 的交联制备多功能 NGs。NG-粘蛋白结合和载多西环素 NG 的抗菌功效研究揭示了 pH 响应和氧化还原线索之间的相互作用。具体来说，较高的 BAC 组成增加了在还原条件下的粘蛋白结合和控制释放，而较高的 BIS 组成则产生了具有更高多西环素介导的针对 的抗菌功效的 NG。研究结果揭示了多响应性 NG 在感染黏膜中有效抗菌药物输送的潜力。
