Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 211198 Nanjing, China.
Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 210023 Nanjing, China; Jiangsu Province Academy of Traditional Chinese Medicine, 210028 Nanjing, China.
Int J Pharm. 2023 Jan 5;630:122419. doi: 10.1016/j.ijpharm.2022.122419. Epub 2022 Nov 21.
In this study, γ-cyclodextrins (γ-CD) and epigallocatechin-3-gallate (EGCG) were designed to form an inclusion complex (EGCG-γ-IC) for ulcerative colitis (UC) treatment. The drug-excipient combined therapeutic potential of γ-CD and EGCG was verified, when stability and compliance were also achieved. EGCG-γ-IC effectively inhibited the secretions of NO, TNF-α, and IL-6 and the intracellular ROS in RAW264.7 cells. The effectiveness of EGCG-γ-IC in treating DSS-induced acute UC in mice was observed including improving the histological conditions of the colon, reducing the levels of IL-1β, IL-6, and TNF-α in serum, and restoring MPO, GSH, and sIgA levels in intestinal tissues. Moreover, EGCG-γ-IC had a more prominent effect on regulating bacterial dysbiosis caused by DSS than EGCG and γ-CD alone. Therefore, EGCG-γ-IC designed here displayed UC treating capacity with safety in the long-term application and promised an industrial production potential due to its excellent storage stability.
在这项研究中,γ-环糊精(γ-CD)和表没食子儿茶素没食子酸酯(EGCG)被设计形成一个包含复合物(EGCG-γ-IC),用于治疗溃疡性结肠炎(UC)。验证了γ-CD 和 EGCG 的药物赋形剂联合治疗潜力,同时还实现了稳定性和顺应性。EGCG-γ-IC 能有效抑制 RAW264.7 细胞中 NO、TNF-α 和 IL-6 的分泌以及细胞内 ROS。观察了 EGCG-γ-IC 对 DSS 诱导的急性 UC 小鼠的治疗效果,包括改善结肠的组织学状况、降低血清中 IL-1β、IL-6 和 TNF-α 的水平,并恢复肠道组织中的 MPO、GSH 和 sIgA 水平。此外,EGCG-γ-IC 对 DSS 引起的细菌失调的调节作用比 EGCG 和 γ-CD 单独作用更为显著。因此,设计的 EGCG-γ-IC 具有长期应用的安全性和治疗 UC 的能力,并因其优异的储存稳定性而具有工业生产潜力。