软骨损伤，尤其是骨关节炎（OA），是一个常见的健康问题，在不同年龄群体中引起疼痛和残疾，尤其是老年人和运动员。在软骨组织修复中需要考虑的主要挑战之一是在活跃的炎症环境中再生软骨组织。槲皮素具有抗炎、抗氧化、凋亡和抑制增殖等多种生物学效应。槲皮素在制药领域的唯一缺点是其在水介质中的不稳定性和低溶解度。本研究旨在制备基于壳聚糖（CS）的纳米颗粒，以提高槲皮素的生物利用度。然后，还研究了槲皮素载药纳米颗粒（FNPs）对白细胞介素-1β（IL-1β）预处理的人软骨细胞的炎症反应的影响。FNPs的平均大小为363.1 ± 17.2nm，静电电位为+17.7 ± 0.1mV，封装效率（EE）和载药量（LC）分别为78.79 ± 7.7%和37.46 ± 6.6%。人软骨细胞的存活率在2000μg/mL浓度以下不受空白纳米颗粒（BNPs）的影响。此外，溶血结果明确表明FNPs不损害红细胞（RBCs），在调查范围内具有良好的血液相容性。与槲皮素类似，FNPs能够抑制IL-1β诱导的炎症反应，如白介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的表达，同时增加抗炎细胞因子白介素-10（IL-10）的产生。总体而言，体外评价结果表明，FNPs可以作为传递槲皮素治疗骨关节炎炎症的传递系统。© 2023. Springer Nature Limited.

Cartilage lesions, especially osteoarthritis (OA), are a common health problem, causing pain and disability in various age groups, principally in older adults and athletes. One of the main challenges to be considered in cartilage tissue repair is the regeneration of cartilage tissue in an active inflammatory environment. Fisetin has various biological effects including anti-inflammatory, antioxidant, apoptotic, and antiproliferative activities. The only disadvantages of fisetin in the pharmaceutical field are its instability and low solubility in aqueous media. This study is aimed at preparing chitosan (CS)-based nanoparticles to yield fisetin with improved bioavailability features. Then, the effect of fisetin-loaded nanoparticles (FNPs) on inflammatory responses in interleukin-1β (IL-1β) pretreated human chondrocytes has also been investigated. FNPs presented an average size of 363.1 ± 17.2 nm and a zeta potential of + 17.7 ± 0.1 mV with encapsulation efficiency (EE) and loading capacity (LC) of 78.79 ± 7.7% and 37.46 ± 6.6%, respectively. The viability of human chondrocytes was not affected by blank nanoparticles (BNPs) up to a concentration of 2000 μg/mL. In addition, the hemolysis results clearly showed that FNPs did not damage the red blood cells (RBCs) and had good hemocompatibility within the range investigated. FNPs, similar to fisetin, were able to inhibit the inflammatory responses induced by IL-1β such as the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) while increasing the production of an anti-inflammatory cytokine such as interleukin-10 (IL-10). Overall, the in vitro evaluation results of the anti-inflammatory activity showed that FNPs can serve as delivery systems to transfer fisetin to treat inflammation in OA.© 2023. Springer Nature Limited.