Pouyanfar Niki, Farnam Golrokh, Ahmadi Mahnaz, Masoudifar Reyhane, Banan Kamran, Asadian Elham, Shahhosseini Soraya, Shahbazi Mohammad-Ali, Shirazi Farshad H, Ghorbani-Bidkorpeh Fatemeh
Department of Pharmaceutics and Pharmaceutical Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Int J Biol Macromol. 2024 Dec;283(Pt 2):137715. doi: 10.1016/j.ijbiomac.2024.137715. Epub 2024 Nov 15.
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation of the joints, leading to pain, swelling, and potential joint destruction. Effective management of RA is crucial to improve patients' quality of life and prevent long-term disability. Methotrexate (MTX) is a widely used disease-modifying antirheumatic drug (DMARD) that has shown efficacy in treating RA. However, its use is often limited by significant adverse effects, particularly on healthy tissues and organs, including hepatotoxicity, myelosuppression, and gastrointestinal complications. Therefore, developing targeted drug delivery systems (DDSs) for MTX is essential to enhance its therapeutic effects while minimizing systemic toxicity. Metal-organic frameworks (MOFs), specifically MIL-100(Fe), present a promising approach for targeted drug delivery in RA treatment due to their high porosity, large surface area, and excellent loading capacity. The acid-responsive properties of MIL-100(Fe) make it particularly suitable for targeting the acidic microenvironment of inflamed joints. In this study, we synthesized MIL-100(Fe) using a microwave-assisted method and embedded MTX within these nanocarriers. The nanocarriers were subsequently coated with chitosan and modified with hyaluronic acid through 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC). Comprehensive characterization techniques such as dynamic light scattering (DLS), zeta potential analysis, Brunauer-Emmett-Teller (BET) surface area measurement, X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), and field emission scanning electron microscopy (FESEM) were employed to evaluate the nanoparticles. Additionally, we assessed cell cytotoxicity and cellular uptake in macrophage cell lines. Overall, the results indicate that the prepared MIL-100(Fe) nanoparticles are a suitable DDS for targeted MTX delivery in RA treatment.
类风湿性关节炎（RA）是一种慢性自身免疫性疾病，其特征是关节炎症，可导致疼痛、肿胀以及潜在的关节破坏。有效管理类风湿性关节炎对于提高患者生活质量和预防长期残疾至关重要。甲氨蝶呤（MTX）是一种广泛使用的改善病情抗风湿药（DMARD），已显示出治疗类风湿性关节炎的疗效。然而，其使用常常受到严重不良反应的限制，特别是对健康组织和器官的影响，包括肝毒性、骨髓抑制和胃肠道并发症。因此，开发针对甲氨蝶呤的靶向给药系统（DDS）对于增强其治疗效果同时最小化全身毒性至关重要。金属有机框架（MOF），特别是MIL-100（Fe），由于其高孔隙率、大表面积和出色的负载能力，在类风湿性关节炎治疗的靶向给药方面呈现出一种有前景的方法。MIL-100（Fe）的酸响应特性使其特别适合靶向炎症关节的酸性微环境。在本研究中，我们使用微波辅助方法合成了MIL-100（Fe），并将甲氨蝶呤嵌入这些纳米载体中。随后用壳聚糖包覆纳米载体，并通过1-乙基-3-（3-二甲基氨基丙基）碳二亚胺（EDC）用透明质酸进行修饰。采用动态光散射（DLS）、zeta电位分析、布鲁诺尔-埃米特-泰勒（BET）表面积测量、X射线衍射（XRD）、傅里叶变换红外光谱（FT-IR）和场发射扫描电子显微镜（FESEM）等综合表征技术来评估纳米颗粒。此外，我们评估了巨噬细胞系中的细胞毒性和细胞摄取。总体而言，结果表明所制备的MIL-100（Fe）纳米颗粒是类风湿性关节炎治疗中靶向递送甲氨蝶呤的合适给药系统。
