Departamento de Biología, Bioquímica y Farmacia, Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), Universidad Nacional del Sur (UNS)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av La Carrindanga Km 7, 8000, Bahía Blanca, Argentina.
Departamento de Química, Instituto de Química del Sur (INQUISUR), UNS-CONICET, Av. Alem 1253, 8000, Bahía Blanca, Argentina.
ChemMedChem. 2024 Nov 18;19(22):e202400321. doi: 10.1002/cmdc.202400321. Epub 2024 Sep 17.
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.
听力损失（HL）影响了全球超过 5%的人口，预计未来几年，年轻人的发病率将高达 50%。由于内耳的密闭性，HL 的治疗方法仍然有限。HL 通常涉及炎症过程，这强调了需要增强对内耳的抗炎药物的递送。我们的研究集中在基于磁性纳米粒子（MNPs）的靶向治疗的开发上。我们之前合成了具有生物相容性的叶酸包覆的氧化铁核纳米粒子（MNPs@FA），作为潜在的抗炎药双氯芬酸（Dfc）载体。本研究旨在将 Dfc 加载到 MNPs@FA 上，以促进靶向内耳给药。通过优化加载程序，我们实现了最佳的载药能力。研究了 Dfc 在模拟靶液和给药载体中的释放情况。还展示了完整的特性。体外细胞相容性测试确保了所得配方的生物安全性。随后对小鼠耳蜗的离体靶向实验验证了纳米系统穿透圆窗膜（HL 治疗的主要障碍之一）的能力。这些发现为继续进行更复杂的体内研究提供了验证。总之，这里呈现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。
