Drug Delivery and Translational Research ( IF 5.7 ) Pub Date : 2022-08-14 , DOI: 10.1007/s13346-022-01221-7 Ravi Raj Pal 1 , Vasundhara Rajpal 2 , Neelu Singh 1 , Sukhveer Singh 3 , Nidhi Mishra 1 , Priya Singh 1 , Priyanka Maurya 1 , Alka 1 , Shubhini A Saraf 1
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Rheumatoid arthritis (RA) is a joint ailment with multi-factorial immune-mediated degenerative pathogenesis, including genetic and environmental defects. Resistance to disease-modifying anti-rheumatic drugs (DMARDs) happens due to excessive drug efflux over time, rendering the concentration insufficient to elicit a response. Thymoquinone (TQ) is a quinone-based phenolic compound with antioxidant and anti-inflammatory activities that downregulate numerous pro-inflammatory cytokines. However, its pharmaceutical importance and therapeutic utility are underexplored due to intrinsic physicochemical characteristics such as inadequate biological stability, short half-life, low hydrophilicity, and less systemic availability. Tamanu oil-stabilised nanostructured lipid carriers (TQ-NLCs) were prepared and optimised using Box-Behnken design (BBD) with the size of 153.9 ± 0.52 nm and surface charge of −30.71 mV. The % entrapment efficiency and drug content were found to be 84.6 ± 0.50% and 14.75 ± 0.52%, respectively. Furthermore, the TQ-loaded NLCs (TQ-NLCs) assayed for skin permeation for transdermal delivery which significantly (p < 0.05) increased skin enhancement ratio 14.6 times compared to the aqueous solution of TQ. Tamanu oil displayed the synergistic anti-inflammatory potential with TQ in comparison to pure TQ, as evidenced against carrageenan (CRG)-induced paw oedema model and Freund’s adjuvant-induced arthritic model. The arthritic and X-ray scores significantly (p < 0.05) reduced in TQ-NLCs and standard formulation-treated groups. Moreover, serum pro-inflammatory marker TNF-α and IL-6 levels were also significantly (p < 0.05) reduced in TQ-NLCs gel-treated group compared to the arthritic control group.
Graphical abstract
中文翻译：
使用基于醌的酚类纳米脂质载体在类风湿性关节炎中下调促炎标志物 IL-6 和 TNF-α：体外和体内研究
类风湿性关节炎 (RA) 是一种关节疾病，具有多因素免疫介导的退行性发病机制，包括遗传和环境缺陷。对改善疾病的抗风湿药 (DMARD) 的耐药性是由于随着时间的推移药物外流过多，导致浓度不足以引起反应。百里醌 (TQ) 是一种基于醌的酚类化合物，具有抗氧化和抗炎活性，可下调多种促炎细胞因子。然而，由于生物稳定性不足、半衰期短、亲水性低和系统利用度低等内在理化特性，其药学重要性和治疗效用尚未得到充分探索。使用 Box-Behnken 设计 (BBD) 制备和优化琼崖海棠油稳定的纳米结构脂质载体 (TQ-NLC)，尺寸为 153.9 ± 0.52 nm，表面电荷为 -30.71 mV。包封率百分比和药物含量分别为 84.6 ± 0.50% 和 14.75 ± 0.52%。此外，载有 TQ 的 NLC (TQ-NLC) 测定了透皮递送的皮肤渗透性，这显着（p < 0.05) 与 TQ 水溶液相比，皮肤增强率增加了 14.6 倍。与纯 TQ 相比，琼崖海棠油显示出与 TQ 的协同抗炎潜力，这在角叉菜胶 (CRG) 诱导的爪水肿模型和弗氏佐剂诱导的关节炎模型中得到了证明。 在 TQ-NLC 和标准制剂治疗组中，关节炎和 X 射线评分显着降低 ( p < 0.05)。 此外，与关节炎对照组相比，TQ-NLCs 凝胶治疗组的血清促炎标志物 TNF-α 和 IL-6 水平也显着降低 ( p < 0.05)。
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