An Mengchen, Shi Mengxiao, Su Jingjing, Wei Yueru, Luo Rongrong, Sun Pengchao, Zhao Yongxing
Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, No. 100 Science Ave, Zhengzhou 450001, China.
Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou University, No. 100 Science Ave, Zhengzhou 450001, China.
Pharmaceutics. 2022 Jul 21;14(7):1518. doi: 10.3390/pharmaceutics14071518.
Although the inhibitors of the interleukin-6 receptor (IL-6R) and tumor necrosis factor-α (TNF-α) have achieved a certain success in the clinical treatment of rheumatoid arthritis (RA), great effort should be made to overcome side effects and to improve patient compliance. The present research aimed to address these problems by the co-delivery of tocilizumab (TCZ)-an inhibitor of IL-6R-and an aptamer Apt1-67, which specifically inhibits TNF receptor 1 via separable microneedles (MN). MN were featured with a sustained release of TCZ from needle tips and a rapid release of Apt1-67 from needle bodies by using methacrylate groups grafted hyaluronic acid as the fillings of needle tips and polyvinyl alcohol/polyvinyl pyrrolidone as the fillings of needle bodies. Our results demonstrated that TCZ and Apt1-67 were distributed in MN as expected, and they could be released to the surroundings in the skin. In vivo studies revealed that combined medication via MN (TCZ/Apt1-67@MN) was superior to MN loaded with a single drug. Compared with subcutaneous injection, TCZ/Apt1-67@MN was of great advantage in inhibiting bone erosion and alleviating symptoms of CIA mice. This study not only provides a novel approach for combined medication with different release properties but also supplies a strategy for improving drug efficacy.
尽管白细胞介素-6受体（IL-6R）抑制剂和肿瘤坏死因子-α（TNF-α）抑制剂在类风湿性关节炎（RA）的临床治疗中取得了一定成效，但仍需付出巨大努力来克服副作用并提高患者依从性。本研究旨在通过共同递送托珠单抗（TCZ）（一种IL-6R抑制剂）和适配体Apt1-67来解决这些问题，Apt1-67可通过可分离微针（MN）特异性抑制肿瘤坏死因子受体1。通过使用接枝甲基丙烯酸酯基团的透明质酸作为针尖填充物、聚乙烯醇/聚乙烯吡咯烷酮作为针体填充物，MN具有从针尖持续释放TCZ以及从针体快速释放Apt1-67的特点。我们的结果表明，TCZ和Apt1-67按预期分布在MN中，并且它们可以释放到皮肤周围环境中。体内研究表明，通过MN联合给药（TCZ/Apt1-67@MN）优于加载单一药物的MN。与皮下注射相比，TCZ/Apt1-67@MN在抑制骨侵蚀和减轻胶原诱导性关节炎（CIA）小鼠症状方面具有很大优势。本研究不仅为具有不同释放特性的联合给药提供了一种新方法，还为提高药物疗效提供了一种策略。
