Zhou Haiyan, Ichikawa Atsuko, Ikeuchi-Takahashi Yuri, Hattori Yoshiyuki, Onishi Hiraku
Department of Drug Delivery Research, Hoshi University, 2-4-41, Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
CMIC Pharma Science Co., Ltd., 10221, Kobuchisawacho, Hokuto 408-0044, Yamanashi, Japan.
Pharmaceutics. 2019 Jul 13;11(7):333. doi: 10.3390/pharmaceutics11070333.
A novel anionic nanogel system was prepared using succinylated glycol chitosan-succinyl prednisolone conjugate (S-GCh-SP). The nanogel, named NG(S), was evaluated in vitro and in vivo. S-GCh-SP formed a nanogel via the aggregation of hydrophobic prednisolone (PD) moieties and the introduced succinyl groups contributed to the negative surface charge of the nanogel. The resultant NG(S) had a PD content of 13.7% (/), was ca. 400 nm in size and had a ζ-potential of -28 mV. NG(S) released PD very slowly at gastric pH and faster but gradually at small intestinal pH. Although NG(S) was easily taken up by the macrophage-like cell line Raw 264.7, it did not decrease cell viability, suggesting that the toxicity of the nanogel was very low. The in vivo evaluation was performed using rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis. NG(S) and PD alone were not very effective at 5 mg PD eq./kg. However, NG(S) at 10 mg PD eq./kg markedly suppressed colonic damage, whereas PD alone did not. Furthermore, thymus atrophy was less with NG(S) than with PD alone. These results demonstrated that NG(S) is very safe, promotes drug effectiveness and has low toxicity. NG(S) has potential as a drug delivery system for the treatment of ulcerative colitis.
使用琥珀酰化壳聚糖-琥珀酰泼尼松龙共轭物（S-GCh-SP）制备了一种新型阴离子纳米凝胶系统。这种名为NG(S)的纳米凝胶进行了体外和体内评估。S-GCh-SP通过疏水性泼尼松龙（PD）部分的聚集形成纳米凝胶，引入的琥珀酰基团赋予了纳米凝胶负表面电荷。所得的NG(S)的PD含量为13.7%（/），尺寸约为400nm，ζ电位为-28mV。NG(S)在胃pH值下非常缓慢地释放PD，在小肠pH值下释放较快但呈逐渐释放。尽管NG(S)很容易被巨噬细胞样细胞系Raw 264.7摄取，但它并没有降低细胞活力，这表明纳米凝胶的毒性非常低。使用三硝基苯磺酸（TNBS）诱导的结肠炎大鼠进行了体内评估。单独使用5mg PD当量/kg的NG(S)和PD效果都不太好。然而，10mg PD当量/kg的NG(S)显著抑制了结肠损伤，而单独使用PD则没有。此外，与单独使用PD相比，NG(S)导致的胸腺萎缩更小。这些结果表明，NG(S)非常安全，能提高药物疗效且毒性低。NG(S)有潜力作为治疗溃疡性结肠炎的药物递送系统。
