Salem Heba F, Abd El-Maboud Marwa Mohamed, Said Amira S A, Salem Mohamed Nabil, Sabry Dina, Hussain Nadia, El-Ghafar Omnia A M Abd, Hussein Raghda R S
Department of Pharmaceutics & Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62521, Egypt.
Department of Clinical Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62521, Egypt.
Pharmaceuticals (Basel). 2022 Dec 31;16(1):60. doi: 10.3390/ph16010060.
Nanomedicine has emerged as an important approach for targeting RA medication. Rheumatoid arthritis (RA) is a widespread autoimmune disorder marked by multiple inflamed joints. Gold nanoparticles (GNPs) have been demonstrated as efficacious nanocarriers due to their unique characteristics and the relative simplicity of their synthesis in varied sizes; moreover, they have the capability to alleviate several inflammatory markers. The current objective was to combine methotrexate (MTX) with GNPs to overcome MTX restrictions. GNPs were fabricated by a chemical reduction technique, utilizing sodium citrate and tween 20. The MTX-GNPs formulations were characterized in vitro by % entrapment efficiency (%EE), particle size, polydispersity index (PDI) zeta potential, and % release. The MTX-GNPs formulation was administrated as an intra-articular solution, and additionally, incorporated into a Carbopol gel to investigate its anti-arthritic effectiveness and bioavailability in vivo. The results indicated that a %EE of 87.53 ± 1.10%, and a particle size of 60.62 ± 2.41 nm with a PDI of 0.31 ± 0.03, and a zeta potential of −27.80 ± 0.36 mV were optimal. The in vitro release of MTX from the MTX-GNPs formulation demonstrated that the MTX-GNPs formulation’s release was 34.91 ± 1.96% and considerably (p < 0.05) lower than that of free MTX, showing a significant difference in dissolution patterns (p < 0.05). In vivo, MTX-GNPs formulations inhibited IL-6 by 36.52%, ACCP (63.25 %), COMP (28.16%), and RANKL (63.67%), as well as elevated IL-10 by 190.18%. Transdermal MTX-GNPs decreased IL-6 by 22.52%, ACCP (56.63%), COMP (52.64%), and RANKL (79.5%), as well as increased IL-10 by 168.37%. Histological investigation supported these recent findings. Conclusions: Marked improvements in MTX anti-arthritic effects are seen when it is conjugated to GNPs.
纳米医学已成为靶向类风湿关节炎药物治疗的一种重要方法。类风湿关节炎（RA）是一种广泛存在的自身免疫性疾病，其特征是多个关节发炎。金纳米颗粒（GNPs）因其独特的特性以及合成不同尺寸时相对简单的方法，已被证明是有效的纳米载体；此外，它们有能力减轻多种炎症标志物。当前的目标是将甲氨蝶呤（MTX）与GNPs结合以克服MTX的局限性。GNPs通过化学还原技术制备，使用柠檬酸钠和吐温20。MTX-GNPs制剂在体外通过包封率（%EE）、粒径、多分散指数（PDI）、zeta电位和释放率进行表征。MTX-GNPs制剂作为关节内溶液给药，此外，还掺入卡波姆凝胶中以研究其在体内的抗关节炎效果和生物利用度。结果表明，最佳包封率为87.53±1.10%，粒径为60.62±2.41nm，多分散指数为0.31±0.03，zeta电位为−27.80±0.36mV。MTX从MTX-GNPs制剂中的体外释放表明，MTX-GNPs制剂的释放率为34.91±1.96%，明显（p<0.05）低于游离MTX，在溶解模式上显示出显著差异（p<0.05）。在体内，MTX-GNPs制剂抑制IL-6达36.52%，抗环瓜氨酸肽（ACCP）达63.25%，软骨寡聚基质蛋白（COMP）达28.16%，核因子κB受体活化因子配体（RANKL）达63.67%，同时使IL-10升高190.18%。经皮给药的MTX-GNPs使IL-6降低22.52%，ACCP降低56.63%，COMP降低52.64%，RANKL降低79.5%，同时使IL-10升高168.37%。组织学研究支持了这些最新发现。结论：当MTX与GNPs偶联时，可以看到其抗关节炎效果有显著改善。
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