Landucci Elisa, Mazzantini Costanza, Calvani Maura, Pellegrini-Giampietro Domenico E, Bergonzi Maria Camilla
Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
Division of Pediatric Oncology/Hematology, Meyer University Children's Hospital, Viale Pieraccini 6, 50139 Florence, Italy.
Pharmaceutics. 2023 Feb 8;15(2):578. doi: 10.3390/pharmaceutics15020578.
Dry eye disease (DED) is a common ocular disorder characterized by an inadequate lubrication of the eye by tears leading to inflammation and the alteration of the ocular surface. Current treatments are often limited due to their side effects and ineffectiveness. Thymoquinone (TQ) is a natural compound present in the essential oil of L., with anti-inflammatory and antioxidant activities. In this study, conventional and hyaluronic acid-coated liposomes were developed to improve TQ activity at ocular level. In the present study, the cytoprotective effects of TQ or TQ liposomes were assessed against oxidative and inflammatory processes in human corneal epithelial cells (HCE-2). Hyperosmolarity conditions (450 mOsm) were used as a model of DED. Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and tumor necrosis factor (TNFα) were quantified by quantitative real-time polymerase chain reaction (RT-qPCR); COX-2 and Phospho-NF-κB p65 (p-p65) by Western blotting (WB). Moreover, the mitochondrial reactive oxygen species (mtROS) levels were measured by MitoSOX assay. The hyperosmotic treatment induced a significant increase of the proinflammatory genes and proteins expression that were significantly decreased in the liposomes-treated cells. The coincubation with hyaluronic acid-coated liposomes significantly reverted the increase of mtROS production, evidently stimulated by the hyperosmotic stress. Our data suggest that TQ-loaded liposomes have potential as a therapeutic agent in dry eye disease, improving the TQ efficacy.
干眼症（DED）是一种常见的眼部疾病，其特征是眼泪对眼睛的润滑不足，导致炎症和眼表改变。目前的治疗方法往往因其副作用和无效性而受到限制。百里醌（TQ）是一种存在于黑种草属植物精油中的天然化合物，具有抗炎和抗氧化活性。在本研究中，开发了常规脂质体和透明质酸包被的脂质体，以提高TQ在眼部的活性。在本研究中，评估了TQ或TQ脂质体对人角膜上皮细胞（HCE-2）氧化和炎症过程的细胞保护作用。高渗条件（450 mOsm）被用作干眼症的模型。通过定量实时聚合酶链反应（RT-qPCR）对白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子（TNFα）进行定量；通过蛋白质免疫印迹法（WB）检测环氧化酶-2（COX-2）和磷酸化核因子-κB p65（p-p65）。此外，通过MitoSOX检测法测量线粒体活性氧（mtROS）水平。高渗处理诱导促炎基因和蛋白表达显著增加，而在脂质体处理的细胞中这些表达显著降低。与透明质酸包被的脂质体共同孵育可显著逆转高渗应激明显刺激的mtROS产生增加。我们的数据表明，负载TQ的脂质体有潜力作为干眼症的治疗药物，提高TQ的疗效。
