Valentino Anna, Conte Raffaele, De Luca Ilenia, Di Cristo Francesca, Peluso Gianfranco, Bosetti Michela, Calarco Anna
Research Institute on Terrestrial Ecosystems (IRET)-CNR, Via Pietro Castellino 111, 80131 Naples, Italy.
AMES Group Polydiagnostic Center, Via Padre Carmine Fico, 24, 80013 Casalnuovo di Napoli, Italy.
Antioxidants (Basel). 2022 Jun 20;11(6):1210. doi: 10.3390/antiox11061210.
Although osteoarthritis (OA) is a chronic inflammatory degenerative disease affecting millions of people worldwide, the current therapies are limited to palliative care and do not eliminate the necessity of surgical intervention in the most severe cases. Several dietary and nutraceutical factors, such as hydroxytyrosol (Hyt), have demonstrated beneficial effects in the prevention or treatment of OA both in vitro and in animal models. However, the therapeutic application of Hyt is limited due to its poor bioavailability following oral administration. In the present study, a localized drug delivery platform containing a combination of Hyt-loading chitosan nanoparticles (Hyt-NPs) and in situ forming hydrogel have been developed to obtain the benefits of both hydrogels and nanoparticles. This thermosensitive formulation, based on Pluronic F-127 (F-127), hyaluronic acid (HA) and Hyt-NPs (called Hyt@tgel) presents the unique ability to be injected in a minimally invasive way into a target region as a freely flowing solution at room temperature forming a gel at body temperature. The Hyt@tgel system showed reduced oxidative and inflammatory effects in the chondrocyte cellular model as well as a reduction in senescent cells after induction with HO. In addition, Hyt@tgel influenced chondrocytes gene expression under pathological state maintaining their metabolic activity and limiting the expression of critical OA-related genes in human chondrocytes treated with stressors promoting OA-like features. Hence, it can be concluded that the formulated hydrogel injection could be proposed for the efficient and sustained Hyt delivery for OA treatment. The next step would be the extraction of "added-value" bioactive polyphenols from by-products of the olive industry, in order to develop a green delivery system able not only to enhance the human wellbeing but also to promote a sustainable environment.
尽管骨关节炎（OA）是一种影响全球数百万人的慢性炎症性退行性疾病，但目前的治疗方法仅限于姑息治疗，在最严重的情况下并不能消除手术干预的必要性。几种饮食和营养因素，如羟基酪醇（Hyt），已在体外和动物模型中证明对OA的预防或治疗具有有益作用。然而，由于口服后生物利用度差，Hyt的治疗应用受到限制。在本研究中，已开发出一种局部给药平台，该平台包含负载Hyt的壳聚糖纳米颗粒（Hyt-NPs）和原位形成水凝胶的组合，以获得水凝胶和纳米颗粒的双重益处。这种基于泊洛沙姆F-127（F-127）、透明质酸（HA）和Hyt-NPs的热敏制剂（称为Hyt@tgel）具有独特的能力，能够在室温下以微创方式作为自由流动的溶液注射到目标区域，并在体温下形成凝胶。Hyt@tgel系统在软骨细胞模型中显示出氧化和炎症作用的降低，以及用HO诱导后衰老细胞的减少。此外，Hyt@tgel在病理状态下影响软骨细胞基因表达，维持其代谢活性，并限制在用促进OA样特征的应激源处理的人软骨细胞中关键OA相关基因的表达。因此，可以得出结论，所配制的水凝胶注射剂可用于OA治疗中高效、持续地递送Hyt。下一步将是从橄榄油工业的副产品中提取“增值”生物活性多酚，以开发一种不仅能够增进人类健康，而且能够促进可持续环境的绿色给药系统。
