Wagle Susbin Raj, Kovacevic Bozica, Ionescu Corina Mihaela, Foster Thomas, Jones Melissa, Mikov Momir, Wise Andrew, Mooranian Armin, Al-Salami Hani
The Biotechnology & Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley 6102, Perth, Western Australia, Australia.
Department of Pharmacology, Toxicology & Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad (Hajduk Veljkova 3, 21101), Serbia.
Ther Deliv. 2024 Apr;15(4):237-252. doi: 10.4155/tde-2023-0099. Epub 2024 Mar 12.
Excessive free radicals contribute to oxidative stress and mitochondrial dysfunction in sensorineural hearing loss (SNHL). The antioxidant probucol holds promise, but its limited bioavailability and inner ear barriers hinder effective SNHL treatment. We addressed this by developing probucol-loaded nanoparticles with polymers and lithocholic acid and tested them on House Ear Institute-Organ of Corti cells. Probucol-based nanoparticles effectively reduced oxidative stress-induced apoptosis, enhanced cellular viability, improved probucol uptake and promoted mitochondrial function. Additionally, they demonstrated the capacity to reduce reactive oxygen species through the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway. This innovative nanoparticle system holds the potential to prevent oxidative stress-related hearing impairment, providing an effective solution for SNHL.
过多的自由基会导致感音神经性听力损失(SNHL)中的氧化应激和线粒体功能障碍。抗氧化剂普罗布考具有一定前景,但其有限的生物利用度和内耳屏障阻碍了对SNHL的有效治疗。我们通过用聚合物和石胆酸制备载有普罗布考的纳米颗粒来解决这一问题,并在House Ear Institute-柯蒂氏器细胞上对其进行了测试。基于普罗布考的纳米颗粒有效降低了氧化应激诱导的细胞凋亡,提高了细胞活力,改善了普罗布考的摄取并促进了线粒体功能。此外,它们还展示了通过核因子红细胞2相关因子2/血红素加氧酶-1途径减少活性氧的能力。这种创新的纳米颗粒系统具有预防氧化应激相关听力损伤的潜力,为SNHL提供了一种有效的解决方案。