State Key Laboratory of Component-based Chinese Medicine, Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, PR China.
Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, PR China.
Drug Deliv. 2021 Dec;28(1):2137-2149. doi: 10.1080/10717544.2021.1986604.
Depression is a primary public health problem. However, current antidepressants work slowly, and together with side effects. Herein, the alginate nanogels were constructed to load albiflorin (albiflorin nanogels), which further formed albiflorin nanogel loaded self-assembled thermosensitive hydrogel system (albiflorin-NGSTH) and were used to improve its antidepressant effects. The nanogel showed a nano-scaled particle size and stronger antioxidant activity. Rheological studies showed that albiflorin-NGSTH had a sol-gel transition at approximately 28 °C. Albiflorin-NGSTH quickly entered the brain by intranasal delivery, and had a continuously release for albiflorin. Preliminary results of mice behavioral despair tests found that albiflorin-NGSTH had no effects on independent exploratory behavior and anxiety of the mice, and significantly decreased immobility duration of the mice in tail suspension test (TST). Moreover, the intranasally administrated albiflorin-NGSTH at a low dose improved depressive behavior, decreased levels of proinflammatory cytokines, and repaired neuronal damage of chronic unpredictable mild stress (CUMS) rats, which indicated an excellent potential for depression therapy. The treatment of albiflorin-NGSTH on depressive disorder was achieved by regulating signal pathway related to depression. Therefore, albiflorin-NGSTH has an excellent potential for clinical application in intranasal drug delivery systems.
抑郁症是一个主要的公共卫生问题。然而，目前的抗抑郁药起效缓慢，且伴有副作用。在此，构建了藻酸盐纳米凝胶来负载白芍总苷（白芍总苷纳米凝胶），进一步形成白芍总苷纳米凝胶载自组装温敏水凝胶系统（albiflorin-NGSTH），用于提高其抗抑郁作用。纳米凝胶显示出纳米级的粒径和更强的抗氧化活性。流变学研究表明，albiflorin-NGSTH 在大约 28°C 时具有溶胶-凝胶转变。通过鼻内给药，albiflorin-NGSTH 迅速进入大脑，并持续释放白芍总苷。小鼠行为绝望试验的初步结果发现，albiflorin-NGSTH 对小鼠的独立探索行为和焦虑没有影响，显著减少了小鼠悬尾试验（TST）中的不动时间。此外，低剂量鼻内给予 albiflorin-NGSTH 可改善慢性不可预测轻度应激（CUMS）大鼠的抑郁行为，降低促炎细胞因子水平，并修复神经元损伤，这表明其在抑郁症治疗方面具有极好的潜力。albiflorin-NGSTH 通过调节与抑郁相关的信号通路来治疗抑郁症。因此，albiflorin-NGSTH 具有在鼻内药物递送系统中临床应用的巨大潜力。
