NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
School of Materials Science and Engineering, Sun Yat-Sen University, Guangzhou, 510275, China.
Adv Sci (Weinh). 2023 Nov;10(33):e2303759. doi: 10.1002/advs.202303759. Epub 2023 Oct 11.
Sepsis is a highly heterogeneous syndrome normally characterized by bacterial infection and dysregulated systemic inflammatory response that leads to multiple organ failure and death. Single anti-inflammation or anti-infection treatment exhibits limited survival benefit for severe cases. Here a biodegradable tobramycin-loaded magnesium micromotor (Mg-Tob motor) is successfully developed as a potential hydrogen generator and active antibiotic deliverer for synergistic therapy of sepsis. The peritoneal fluid of septic mouse provides an applicable space for Mg-water reaction. Hydrogen generated sustainably and controllably from the motor interface propels the motion to achieve active drug delivery along with attenuating hyperinflammation. The developed Mg-Tob motor demonstrates efficient protection from anti-inflammatory and antibacterial activity both in vitro and in vivo. Importantly, it prevents multiple organ failure and significantly improves the survival rate up to 87.5% in a high-grade sepsis model with no survival, whereas only about half of mice survive with the individual therapies. This micromotor displays the superior therapeutic effect of synergistic hydrogen-chemical therapy against sepsis, thus holding great promise to be an innovative and translational drug delivery system to treat sepsis or other inflammation-related diseases in the near future.
脓毒症是一种高度异质的综合征,通常以细菌感染和系统炎症反应失调为特征,导致多器官衰竭和死亡。单一的抗炎或抗感染治疗对严重病例的生存获益有限。在这里,我们成功开发了一种可生物降解的妥布霉素负载镁微马达(Mg-Tob 马达),作为一种潜在的氢气发生器和活性抗生素输送器,用于脓毒症的协同治疗。脓毒症小鼠的腹腔液为 Mg 与水的反应提供了一个适用的空间。从马达界面持续、可控地产生的氢气推动运动,实现了主动药物输送,并减轻了过度炎症。所开发的 Mg-Tob 马达在体外和体内均表现出高效的抗炎和抗菌活性。重要的是,它可以防止多器官衰竭,并在没有生存的情况下,在高等级脓毒症模型中显著提高了 87.5%的存活率,而单独治疗的小鼠只有大约一半存活。这种微马达显示了协同氢化学疗法对脓毒症的优越治疗效果,因此有望成为一种创新的、可转化的药物输送系统,用于治疗脓毒症或其他炎症相关疾病。