Department of Drug Delivery Research, Hoshi University, Tokyo, Japan.
Drug Deliv. 2021 Dec;28(1):144-152. doi: 10.1080/10717544.2020.1865478.
Although prednisolone (PD) is used as an anti-arthritis drug due to its rapid and strong anti-inflammatory potential, its frequent and large dosing often brings about adverse effects. Therefore, targeting therapy has attracted increasing attention to overcome such adverse effects. In the present study, nanogels (NGs) composed of macromolecule-PD conjugates were developed as a novel targeting delivery system, and their anti-inflammatory potential was examined. Conjugates were prepared by carbodiimide coupling between glycyl-prednisolone (GP) and the natural anionic polysaccharides, alginic acid (AL) and hyaluronic acid (HA). NGs were produced by the evaporation of organic solvent from the conjugate solution. The obtained NGs, named AL-GP-NG and HA-GP-NG, respectively, were examined for particle characteristics, release, pharmacokinetics, and efficacy. Both NGs were several hundred nanometers in size, had negative zeta potentials, and several % (w/w) drug contents. They released PD gradually at pH 7.4 and 6. They exhibited fairly good retention in the systemic circulation. In the efficacy examination using rats with adjuvant-induced arthritis, both NGs showed the stronger and more prolonged suppression of paw inflammation than PD alone. These suggested that the present NGs should be possibly useful as anti-arthritis targeting therapeutic systems.
虽然泼尼松龙（PD）因其具有快速和强大的抗炎潜力而被用作抗关节炎药物，但由于其频繁且大剂量使用，常带来不良反应。因此，靶向治疗越来越受到关注，以克服这些不良反应。在本研究中，开发了由大分子 PD 缀合物组成的纳米凝胶（NGs）作为一种新型靶向递药系统，并对其抗炎潜力进行了研究。缀合物是通过碳二亚胺将甘氨酰泼尼松龙（GP）与天然阴离子多糖，即海藻酸钠（AL）和透明质酸（HA）偶联而成。NGs 是通过从缀合物溶液中蒸发有机溶剂而产生的。所得的 NGs 分别命名为 AL-GP-NG 和 HA-GP-NG，对其颗粒特性、释放、药代动力学和功效进行了研究。两种 NGs 的粒径均为数百纳米，具有负的 ζ 电位，且载药率为百分之几（w/w）。它们在 pH 7.4 和 6 下可逐渐释放 PD。在佐剂诱导关节炎大鼠的功效研究中，两种 NGs 均表现出比 PD 单独使用更强和更持久的抑制足爪炎症的作用。这些结果表明，本研究中的 NGs 可能作为抗关节炎靶向治疗系统具有应用潜力。
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