Signorini Sara, Pescina Silvia, Ricci Caterina, Del Favero Elena, Vivero-Lopez Maria, Alvarez-Lorenzo Carmen, Santi Patrizia, Padula Cristina, Nicoli Sara
ADDRes Lab, Department of Food and Drug, University of Parma, Parco Area Delle Scienze 27/a, 43124, Parma, Italy.
Department of Medical Biotechnologies and Translational Medicine, LITA, University of Milan, 20054, Segrate, MI, Italy.
Drug Deliv Transl Res. 2025 Jul;15(7):2415-2430. doi: 10.1007/s13346-024-01739-y. Epub 2024 Dec 7.
Coenzyme Q10 (CoQ10) is a lipophilic antioxidant agent that plays a crucial role in the mitochondrial electron transport chain. The neuroprotective role of CoQ10, countering mitochondrial dysfunction and oxidative stress, suggests its potential as an adjuvant for ocular neurodegenerative diseases linked to retinal cell loss. However, despite its promising properties, ocular barriers pose challenges for effective delivery. Therefore, the present work aimed to identify new ocular delivery strategies to improve the therapeutic potential of CoQ10 by increasing its ocular bioavailability at the posterior segment and supporting its controlled release. Polymeric micelles of D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) were selected as carriers for the loading of CoQ10, increasing its solubility and promoting its penetration through ocular tissues. After their characterization by dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS), loaded micelles were applied to porcine sclera and choroid to confirm their ex vivo retention and permeation capacity. To ensure a controlled release, they were then loaded into a crosslinked polymer film, which was characterized in terms of mechanical properties, swelling degree and release profiles of TPGS and CoQ10. The biocompatibility of this platform was tested by the HET-CAM assay, and ex vivo studies confirmed its ocular potential.
辅酶Q10（CoQ10）是一种亲脂性抗氧化剂，在线粒体电子传递链中起着关键作用。CoQ10具有神经保护作用，可对抗线粒体功能障碍和氧化应激，这表明它有潜力作为与视网膜细胞丢失相关的眼部神经退行性疾病的辅助治疗药物。然而，尽管CoQ10具有良好的特性，但眼部屏障对其有效递送构成了挑战。因此，本研究旨在确定新的眼部递送策略，通过提高CoQ10在眼后段的眼部生物利用度并支持其控释，来提高CoQ10的治疗潜力。选择琥珀酸聚乙二醇1000维生素E（TPGS）的聚合物胶束作为负载CoQ10的载体，增加其溶解度并促进其穿透眼部组织。通过动态光散射（DLS）和小角X射线散射（SAXS）对其进行表征后，将负载的胶束应用于猪巩膜和脉络膜，以确认其体外滞留和渗透能力。为确保控释，随后将它们负载到交联聚合物薄膜中，该薄膜在机械性能、溶胀度以及TPGS和CoQ10的释放曲线方面进行了表征。通过鸡胚绒毛尿囊膜（HET-CAM）试验测试了该平台的生物相容性，体外研究证实了其眼部应用潜力。
