Abstract：
Hearing loss (HL) affects more than 5% of the global population, with projections indicating an impact of up to 50% on young individuals in the next years. HL treatments remain limited due to the inner ear\'s hermeticism. HL often involves inflammatory processes, underscoring the need for enhanced delivery of antiinflammatory agents to the inner ear. Our research focuses on the development of a directed therapy based on magnetic nanoparticles (MNPs). We previously synthesized biocompatible folic acid-coated iron oxide-core nanoparticles (MNPs@FA) as potential carriers for the anti-inflammatory Diclofenac (Dfc). This study aims to incorporate Dfc onto MNPs@FA to facilitate targeted drug delivery to the inner ear. Through optimizing the loading procedure, we achieved optimal loading capacity. Dfc release was studied in the simulated target fluid and the administration vehicle. Complete characterization is also shown. In vitro biocompatibility testing ensured the biosafety of the resulting formulation. Subsequent ex vivo targeting assays on murine cochleae validated the nanosystems\' ability to penetrate the round window membrane, one of the main HL therapy barriers. These findings serve as validation before continuing to more complex in vivo studies. Together, the data here presented represent an advancement in addressing unmet medical needs in HL therapy.
摘要：
听力损失（HL）影响全球5%以上的人口，预测显示未来几年对年轻人的影响高达50%。由于内耳的封闭性，HL治疗仍然有限。HL通常涉及炎症过程，强调需要加强向内耳递送抗炎药。我们的研究重点是开发基于磁性纳米粒子（MNPs）的定向疗法。我们先前合成了生物相容性叶酸包覆的氧化铁核纳米颗粒（MNPs@FA）作为抗炎双氯芬酸（Dfc）的潜在载体。这项研究旨在将Dfc掺入到MNPs@FA上，以促进药物靶向递送到内耳。通过优化加载程序，我们实现了最佳的装载能力。在模拟目标流体和给药载体中研究Dfc释放。还显示了完整的表征。体外生物相容性测试确保了所得制剂的生物安全性。随后对小鼠耳蜗的离体靶向试验验证了纳米系统穿透圆窗膜的能力，HL治疗的主要障碍之一。这些发现在继续进行更复杂的体内研究之前作为验证。一起,此处提供的数据代表了在解决HL治疗中未满足的医疗需求方面的进展.
