Abstract

The study planned to estimate biological parameters linked to rheumatoid arthritis (RA) patients, detecting the influence of MTX and biotherapy treatments on these parameters and synthesizing methotrexate bovine serum albumin nanoparticles linked to folate (FA-MTX-BSA NPs) to reduce the overwhelming expression of inflammatory cytokines. Inflammatory parameters showed significant increases in newly diagnosed and MTX-receiving groups while no changes were observed in the biotherapy-maintained group. MTX-loaded BSA nanoparticles were fabricated by the desolvation method and further linked to activated folic acid to obtain FA-MTX-BSA NPs. FA-MTX-BSA NPs were successfully characterized within the nanoscale range using different screening techniques. FA-MTX-BSA NPs showed an in vitro release in a sustained manner. The potential of MTX, MTX-BSA NPs, and FA-MTX-BSA NPs in inducing cytokine level reduction was detected. Significant decreases in interleukin- 1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels were obtained in cultures treated with FA-MTX-BSA NPs compared to the untreated culture in a dose-dependent pattern. Furthermore, FA-MTX-BSA NPs comparing with MTX and MTX-BSA NPs exhibited a significant advanced effect in decreasing cytokines levels. Accordingly, the conjunction of BSA NPs and MTX linked to folate potentially reduced cytokines manifestation in RA.

摘要

该研究计划估计与类风湿性关节炎 (RA) 患者相关的生物学参数，检测 MTX 和生物治疗对这些参数的影响，并合成与叶酸相关的甲氨蝶呤牛血清白蛋白纳米颗粒 (FA-MTX-BSA NPs) 以减少压倒性表达的炎性细胞因子。炎症参数在新诊断组和接受 MTX 组中显着增加，而在生物治疗维持组中没有观察到变化。通过去溶剂化法制备载有 MTX 的 BSA 纳米颗粒，并进一步与活化的叶酸连接以获得 FA-MTX-BSA 纳米颗粒。使用不同的筛选技术在纳米级范围内成功表征了 FA-MTX-BSA NP。FA-MTX-BSA NPs在体外表现出持续释放。检测了 MTX、MTX-BSA NPs 和 FA-MTX-BSA NPs 在诱导细胞因子水平降低方面的潜力。与未处理的相比，在用 FA-MTX-BSA NP 处理的培养物中，白细胞介素 1 β (IL-1β)、白细胞介素 6 (IL-6) 和肿瘤坏死因子-α (TNF-α) 水平显着降低以剂量依赖模式培养。此外，与 MTX 和 MTX-BSA NPs 相比，FA-MTX-BSA NPs 在降低细胞因子水平方面表现出显着的先进作用。因此，与叶酸相关的 BSA NP 和 MTX 的结合可能会减少 RA 中细胞因子的表现。