School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Nantong First People's Hospital, Nantong, 226001, China.
J Nanobiotechnology. 2021 Dec 7;19(1):409. doi: 10.1186/s12951-021-01157-z.
Attenuating inflammatory response and relieving pain are two therapeutic therapeutical goals for rheumatoid arthritis (RA). Anti-inflammatory and analgesic drugs are often associated with many adverse effects due to nonspecific distribution. New drug delivery systems with practical targeting ability and other complementary strategies urgently need to be explored. To achieve this goal, an acupoint drug delivery system that can target deliver anti-inflammatory drugs and simulate acupuncture in relieving pain was constructed, which can co-deliver triptolide (TP) and 2-chloro-N (6)-cyclopentyl adenosine (CCPA).
We have successfully demonstrated that acupoint nanocomposite hydrogel composed of TP-Human serum album nanoparticles (TP@HSA NPs) and CCPA could effectively treat RA. The result shows that CCPA-Gel can enhance analgesic effects specifically at the acupoint, while the mechanical and thermal pain threshold was 4.9 and 1.6 times compared with non-acupoint, respectively, and the nanocomposite gel further enhanced. Otherwise, the combination of acupoint and nanocomposite hydrogel exerted synergetic improvement of inflammation, bone erosion, and reduction of systemic toxicity. Furthermore, it could regulate inflammatory factors and restore the balance of Th17/Treg cells, which provided a novel and effective treatment strategy for RA. Interestingly, acupoint administration could improve the accumulation of the designed nanomedicine in arthritic paws (13.5% higher than those in non-acupoint at 48 h), which may explain the better therapeutic efficiency and low toxicity.
This novel therapeutic approach-acupoint nanocomposite hydrogel, builds a bridge between acupuncture and drugs which sheds light on the combination of traditional and modern medicine.
减轻炎症反应和缓解疼痛是类风湿关节炎(RA)的两个治疗目标。由于非特异性分布,抗炎和镇痛药物通常与许多不良反应相关。因此,迫切需要探索具有实际靶向能力的新药物传递系统和其他互补策略。为了实现这一目标,构建了一种能够靶向传递抗炎药物并模拟针刺缓解疼痛的穴位药物传递系统,该系统可以共递送雷公藤内酯醇(TP)和 2-氯-N(6)-环戊基腺苷(CCPA)。
我们已经成功地证明,由 TP-人血清白蛋白纳米粒(TP@HSA NPs)和 CCPA 组成的穴位纳米复合水凝胶可以有效地治疗 RA。结果表明,CCPA-凝胶可以特异性地增强穴位的镇痛作用,而机械和热痛阈值分别比非穴位高 4.9 和 1.6 倍,纳米复合凝胶进一步增强。此外,穴位与纳米复合水凝胶的联合作用协同改善了炎症、骨质侵蚀,并降低了全身毒性。此外,它还可以调节炎症因子并恢复 Th17/Treg 细胞的平衡,为 RA 提供了一种新的有效治疗策略。有趣的是,穴位给药可以提高设计的纳米药物在关节炎爪子中的积累(48 小时时比非穴位高 13.5%),这可能解释了更好的治疗效果和低毒性。
这种新的治疗方法——穴位纳米复合水凝胶,在针灸和药物之间架起了一座桥梁,为传统医学与现代医学的结合提供了思路。