Abstract

The efficacy of alginate-glycyl-prednisolone conjugate nanogel (AL-GP-NG) was previously reported to be better than that of prednisolone (PD) alone in arthritic rats. In the present study, novel AL-GP-NG was prepared and its targeting potential was investigated. AL-GP-NG with a PD content of 6.3% (w/w) was obtained and had a slightly larger submicron size and similar zeta potential to that of the previous nanogel. Drug release profiles and pharmacokinetic features were similar to those of the previous nanogel. AL-GP-NG showed prolonged release at weakly acidic and neutral pH and the good systemic retention of total (free + conjugated) PD after an intravenous (i.v.) injection in rats. In animal studies using normal and adjuvant-induced arthritic rats, the distribution of total PD was examined after an i.v. injection. AL-GP-NG achieved a markedly higher drug concentration at inflamed joints than PD alone. Furthermore, ALGP-NG showed specific drug localisation to inflamed joints in arthritic rats, but not in normal rats. Furthermore, specific drug localisation to the joints by AL-GP-NG persisted. Collectively, these results demonstrated the good targeting potential of AL-GP-NG to inflamed joints, suggesting its suitability for the treatment of arthritis.

摘要

先前报道，海藻酸盐-甘氨酰-泼尼松龙缀合物纳米凝胶 (AL-GP-NG) 的疗效优于单独使用泼尼松龙 (PD) 在关节炎大鼠中的疗效。在本研究中，制备了新型 AL-GP-NG 并研究了其靶向潜力。获得了 PD 含量为 6.3% (w/w) 的 AL-GP-NG，其亚微米尺寸略大，zeta 电位与之前的纳米凝胶相似。药物释放曲线和药代动力学特征与之前的纳米凝胶相似。AL-GP-NG 在弱酸性和中性 pH 值下表现出延长释放，并且在大鼠静脉内 (iv) 注射后总（游离 + 结合）PD 的良好全身保留。在使用正常和佐剂诱导的关节炎大鼠的动物研究中，在静脉注射后检查总 PD 的分布。AL-GP-NG 在发炎关节处的药物浓度明显高于单独的 PD。此外，ALGP-NG 在关节炎大鼠的发炎关节中显示出特异性的药物定位，但在正常大鼠中则没有。此外，AL-GP-NG 对关节的特定药物定位持续存在。总的来说，这些结果证明了 AL-GP-NG 对发炎关节的良好靶向潜力，表明其适用于治疗关节炎。