An ameliorated anti-hTNF-α therapy for arthritis via carrier-free macromolecular nanoparticles consisted of infliximab
An ameliorated anti-hTNF-α therapy for arthritis via carrier-free macromolecular nanoparticles consisted of infliximab
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DOI：
10.1016/j.ijpharm.2022.122414
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发表时间：
2022-11-25
影响因子：
5.8
通讯作者：
Zhang，Qiang
中科院分区：
文献类型：
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作者：
Li，Yong;Wang，Xueqing;Zhang，Qiang
英夫利昔单抗（INF）静脉注射用于类风湿性关节炎的临床治疗。然而，它会引起严重的副作用，这主要与全身暴露和高剂量有关。在这里，我们通过将带相反电荷的牛乳铁蛋白（BLF）和透明质酸（HA）依次引入到INF溶液中，开发了一种改性的疏水离子配对复合物（INF HIPC）。研究发现，INF和BLF不仅对HIPC的结构完整性负责，而且通过结合人肿瘤坏死因子-α (hTNF-α)或促进成骨细胞的增殖，确定了各自的生物活性。该方法稳定性好，载药效率高，具有长期保留效果。无论是通过膝关节注射还是静脉注射，在转基因小鼠模型中，INF HIPC导致hTNF-α水平低于INF，软骨破坏程度低于INF。同时，INF - HIPC可以根据转基因小鼠的体重变化来降低毒性。我们的发现为开发其他抗体和大分子的先进递送系统提供了一种简单而有前途的途径。
Infliximab (INF) is intravenously used for the clinical treatment of rheumatoid arthritis. However, it can cause serious side effects, which are mainly associated with systemic exposure and high doses. Here, we developed a modified hydrophobic ion-pairing complexes (INF HIPC) through the sequential introduction of bovine lactoferrin (BLF) and hyaluronic acid (HA) with opposite charges into the INF solution. INF and BLF were found to be not only integrally responsible for the structural integrity of HIPC but also were determined to have respective biological activities by binding human tumor necrosis factor-alpha (hTNF-α) or promoting the proliferation of osteoblasts. The INF HIPC had good stability, high drug-loading efficiency, and long-term retention effects. Whether via knee joint injection or intravenous injection, INF HIPC resulted in lower hTNF-α levels and less cartilage destruction than INFs in the transgenic mouse model. At the same time, INF HIPC could reduce toxicity based on body weight changes in transgenic mice. Our findings provide a simple and promising avenue to develop advanced delivery systems for other antibodies and macromolecules.