Cao Jian, Zhang Nan, Wang Ziyi, Su Jingjing, Yang Jing, Han Jiabing, Zhao Yongxing
Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou 450001, China.
Pharmaceutics. 2019 May 15;11(5):235. doi: 10.3390/pharmaceutics11050235.
Rheumatoid arthritis (RA) is a complicated autoimmune disease. The clinical applications of etanercept (EN), a TNF-α inhibitor, can efficiently halt the development of RA. EN is mainly administrated by subcutaneous injection, which may cause low compliance, side effects, and infection risk. In this study, a hyaluronic acid crosslinked microneedle system (MN) was constructed as the transdermal alternative to deliver EN. We describe the formulation, fabrication, characterization, and transdermal insertion study of MN. In vitro bioactivity of EN was conducted and analyzed by dynamic light scattering and circular dichroism spectrum. In vivo evaluation of MN was studied on adjuvant-induced arthritis mice. The MN possessed sufficient mechanical strength, good biocompatibility, little influence on the bioactivity of EN, and high anti-inflammatory efficacy. This work represents a successful example of delivering macromolecule therapeutic treatment by MN for RA treatment. The transdermal delivery of EN by MN offers a new treatment option for RA patients.
类风湿关节炎（RA）是一种复杂的自身免疫性疾病。肿瘤坏死因子-α抑制剂依那西普（EN）的临床应用能够有效阻止RA的发展。EN主要通过皮下注射给药，这可能导致依从性低、副作用以及感染风险。在本研究中，构建了一种透明质酸交联微针系统（MN）作为EN的经皮给药替代方案。我们描述了MN的配方、制备、表征以及经皮插入研究。通过动态光散射和圆二色光谱对EN进行体外生物活性测定和分析。在佐剂诱导的关节炎小鼠上对MN进行体内评估。该MN具有足够的机械强度、良好的生物相容性，对EN的生物活性影响小，且具有高抗炎功效。这项工作是通过MN递送大分子治疗药物用于RA治疗的成功范例。MN经皮递送EN为RA患者提供了一种新的治疗选择。
