Citation: Yu Yan, Jiawei Song, Dongdong Liu, Zihan Liu, Jialing Cheng, Zhiyang Chen, Yanfang Yang, Weizhe Jiang, Hongliang Wang, Jun Ye, Yuling Liu. Simple and versatile in situ thermo-sensitive hydrogel for rectal administration of SZ-A to alleviate inflammation and repair mucosal barrier in ulcerative colitis[J]. Chinese Chemical Letters, ;2024, 35(6): 109736. doi: 10.1016/j.cclet.2024.109736 shu

Simple and versatile in situ thermo-sensitive hydrogel for rectal administration of SZ-A to alleviate inflammation and repair mucosal barrier in ulcerative colitis

Yu Yan ^{a, b, c, 1} ,
Jiawei Song ^{a, c, 1} ,
Dongdong Liu ^{a, b, c} ,
Zihan Liu ^{a, c} ,
Jialing Cheng ^{a, c} ,
Zhiyang Chen ^{a, c} ,
Yanfang Yang ^{a, c} ,
Weizhe Jiang ^b ,
Hongliang Wang ^{a, c, *,} ,
Jun Ye ^{a, c, *,} ,
Yuling Liu ^{a, c, *,}

a.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
b.
College of Pharmacy, Guangxi Medical University, Nanning 530021, China
c.
Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China

wanghl@imm.ac.cn

yelinghao@imm.ac.cn

ylliu@imm.ac.cn

Received Date: 25 January 2024
Revised Date: 1 March 2024
Accepted Date: 5 March 2024
Available Online: 6 March 2024

Figures(3)

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon and disrupted intestinal function. Ramulus mori (Sangzhi) alkaloids (SZ-A), derived from twigs of mulberry, were approved by the National Medical Products Administration in 2020 for treating type 2 diabetes mellitus. Accumulated evidence has confirmed that SZ-A also alleviates non-alcoholic fatty liver disease and ameliorates inflammation, indicating its potential to address inflammation in UC. However, the treatment of UC faces challenges due to low drug delivery efficiency and short retention time. To overcome these challenges, an injectable and adherent in-situ thermo-sensitive hydrogel containing SZ-A was developed for rectal drug delivery, utilizing the thermo-sensitive polymers Poloxamer 407 and 188. The thermo-sensitive hydrogel system was designed with a moderate gelation temperature of 32 ± 0.5 ℃, a short gelation time of 64 s, a pH range of 7–10, high moisturizing capability exceeding 90%, and moderate mechanical strength of 4–5 s. In a rat model with UC, the in situ thermo-sensitive hydrogel significantly extended the retention time at the colonic site and enabled sustained release after rectal administration. Symptoms of UC were markedly reduced following rectal administration of SZ-A thermo-sensitive hydrogel. Furthermore, the release of inflammatory factors, such as interleukin-1β (IL-1β), IL-6, IL-18, tumor necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1), significantly decreased in the SZ-A thermo-sensitive hydrogel group. The integrity of the colonic mucosal barrier was significantly enhanced following the application of SZ-A thermo-sensitive hydrogel. In conclusion, rectal administration of SZ-A in situ thermo-sensitive hydrogel effectively alleviated UC symptoms, inhibited the secretion of inflammatory factors, and promoted the repair of the colonic mucosal barrier. This approach holds promise as a potential treatment for UC.
- Ulcerative colitis,
- SZ-A,
- Thermo-sensitive hydrogel,
- Rectal administration,
- Alleviation of inflammation,
- Mucosal barrier repair
1. [1]
  Y. Liu, B.G. Li, Y.H. Su, et al., J. Ethnopharmacol. 289 (2022) 115084. doi: 10.1016/j.jep.2022.115084
2. [2]
  D. Muthas, A. Reznichenko, C.A. Balendran, et al., Scand J. Gastroenterol. 52 (2017) 125–135.
3. [3]
  H. Shi, X. Zhao, J. Gao, et al., Chin. Chem. Lett. 31 (2020) 3102–3106. doi: 10.1016/j.cclet.2020.03.039
4. [4]
  T. Kucharzik, S. Koletzko, K. Kannengiesser, A. Dignass, Dtsch. Arztebl Int. 117 (2020) 564–574.
5. [5]
  T. Kobayashi, B. Siegmund, C. Le Berre, et al., Nat. Rev. Dis. Prim. 6 (2020) 74. doi: 10.1038/s41572-020-0205-x
6. [6]
  Z. Liu, H. Liu, J. Cheng, et al., Chin. Chem. Lett. 35 (2024) 109074. doi: 10.1016/j.cclet.2023.109074
7. [7]
  Y. Ye, Z. Pang, W. Chen, S. Ju, C. Zhou, Int. J. Clin. Exp. Med. 8 (2015) 22529–22542.
8. [8]
  M.F. Neurath, M. Leppkes, Semin. Immunopathol. 41 (2019) 747–756. doi: 10.1007/s00281-019-00751-6
9. [9]
  R. Ungaro, S. Mehandru, P.B. Allen, L. Peyrin-Biroulet, J.F. Colombel, Lancet 389 (2017) 1756–1770. doi: 10.1016/S0140-6736(16)32126-2
10. [10]
  S. Danese, G. Roda, L. Peyrin-Biroulet, Nat. Rev. Gastroenterol. Hepatol. 17 (2020) 1–2. doi: 10.1038/s41575-019-0211-1
11. [11]
  B. Gros, G.G. Kaplan, JAMA 330 (2023) 951–965. doi: 10.1001/jama.2023.15389
12. [12]
  Y. Cui, T. Zhu, X. Zhang, et al., Chin. Chem. Lett. 33 (2022) 4617–4622. doi: 10.1016/j.cclet.2022.03.077
13. [13]
  M. Kayal, S. Shah, J. Clin. Med. 9 (2019) 94. doi: 10.3390/jcm9010094
14. [14]
  C. Mowat, A. Cole, A. Windsor, et al., Gut 60 (2011) 571–607. doi: 10.1136/gut.2010.224154
15. [15]
  C. Zhang, J. Li, M. Xiao, et al., Chin. Chem. Lett. 33 (2022) 4924–4929. doi: 10.1016/j.cclet.2022.03.110
16. [16]
  M. Sun, W. Ban, H. Ling, et al., Chin. Chem. Lett. 33 (2022) 4449–4460. doi: 10.1016/j.cclet.2022.03.061
17. [17]
  L. Herrera Estrada, H. Wu, K. Ling, et al., ACS Nano 11 (2017) 9650–9662. doi: 10.1021/acsnano.7b03239
18. [18]
  C. Li, Y. Zhao, J. Cheng, et al., Adv. Sci. 6 (2019) 1900610. doi: 10.1002/advs.201900610
19. [19]
  Q. Liu, S. Liu, H. Cao, et al., Front. Pharmacol. 12 (2021) 642400. doi: 10.3389/fphar.2021.642400
20. [20]
  H. Cao, W. Ji, Q. Liu, et al., J. Ethnopharmacol. 280 (2021) 114483. doi: 10.1016/j.jep.2021.114483
21. [21]
  L. Qu, X.C. Liang, G.Q. Tian, et al., Chin. J. Integr. Med. 28 (2022) 304–311. doi: 10.1007/s11655-021-2885-9
22. [22]
  Y.M. Chen, C.F. Lian, Q.W. Sun, et al., Antioxidants 11 (2022) 905. doi: 10.3390/antiox11050905
23. [23]
  T.J. Purohit, S.M. Hanning, Z. Wu, Pharm. Dev. Technol. 23 (2018) 942–952. doi: 10.1080/10837450.2018.1484766
24. [24]
  L.M. Chiang, H.S. Wang, H.H. Shen, et al., Pediatr. Neonatol. 52 (2011) 30–33. doi: 10.1016/j.pedneo.2010.12.009
25. [25]
  J. Shi, L. Yu, J. Ding, Acta Biomater. 128 (2021) 42–59. doi: 10.1016/j.actbio.2021.04.009
26. [26]
  A.D. Drozdov, J.D. Christiansen, J. Mech. Behav. Biomed. Mater. 114 (2021) 104215. doi: 10.1016/j.jmbbm.2020.104215
27. [27]
  Y. Liu, X. Wang, Y. Liu, X. Di, AAPS PharmSciTech 19 (2018) 338–347. doi: 10.1208/s12249-017-0839-5
28. [28]
  Y. Chen, J.H. Lee, M. Meng, et al., Materials 14 (2021) 4522. doi: 10.3390/ma14164522
29. [29]
  W. Boonlai, V. Tantishaiyakul, N. Hirun, T. Sangfai, K. Suknuntha, AAPS Pharm- SciTech 19 (2018) 2103–2117. doi: 10.1208/s12249-018-1010-7
30. [30]
  B. Shriky, A. Kelly, M. Isreb, et al., J. Colloid Interface Sci. 565 (2020) 119–130. doi: 10.1016/j.jcis.2019.12.096
31. [31]
  Y. Petkova-Olsson, C. Oelschlaeger, H. Ullsten, L. Järnström, J. Colloid Interface Sci. 514 (2018) 459–467. doi: 10.1016/j.jcis.2017.12.051
32. [32]
  I. Jarak, C.L. Varela, E. Tavares da Silva, et al., Eur. J. Med. Chem. 206 (2020) 112526. doi: 10.1016/j.ejmech.2020.112526
33. [33]
  M.I. Malik, S. Lee, T. Chang, J. Chromatogr. A 1442 (2016) 33–41. doi: 10.1016/j.chroma.2016.03.008
34. [34]
  P. Xue, L. Wang, J. Xu, et al., Int. J. Pharm. 589 (2020) 119846. doi: 10.1016/j.ijpharm.2020.119846
35. [35]
  S.J. Buwalda, K.W. Boere, P.J. Dijkstra, et al., J. Control. Release 190 (2014) 254–273. doi: 10.1016/j.jconrel.2014.03.052
36. [36]
  J. Wu, J. Zhu, C. He, et al., ACS Appl. Mater. Interfaces 8 (2016) 18710–18721. doi: 10.1021/acsami.6b06047
37. [37]
  S. Rençber, S.Y. Karavana, Z.A. Şenyiğit, et al., Pharm. Dev. Technol. 22 (2017) 551–561. doi: 10.3109/10837450.2016.1163385
38. [38]
  S.Y. Karavana, Z.A. Şenyiğit, Ç. Çalışkan, et al., Drug Des. Devel. Ther. 12 (2018) 1959–1975. doi: 10.2147/DDDT.S164704
39. [39]
  M.A. Fathalla, Z.A. Vangala, M. Longman, et al., Eur. J. Pharm. Biopharm. 114 (2017) 119–134. doi: 10.1016/j.ejpb.2017.01.008
40. [40]
  E. Ban, C.K. Kim, Arch. Pharm. Res. 36 (2013) 586–592. doi: 10.1007/s12272-013-0049-y
41. [41]
  S. Yogev, A. Shabtay-Orbach, A. Nyska, B. Mizrahi, Toxicol. Pathol. 47 (2018) 426–432.
42. [42]
  T. Karaca, Y.H. Uz, S. Demirtas, I. Karaboga, G. Can, Iran. J. Basic Med. Sci. 18 (2015) 370–379.
43. [43]
  G. Wang, Q. Li, D. Chen, et al., Theranostics 9 (2019) 6191–6208. doi: 10.7150/thno.37538
44. [44]
  J. Wang, C. Zhang, C. Guo, X. Li, Int. J. Mol. Sci. 20 (2019) 5751. doi: 10.3390/ijms20225751
45. [45]
  W. Ding, H. Lin, X. Hong, D. Ji, F. Wu, Toxicology 436 (2020) 152437. doi: 10.1016/j.tox.2020.152437
46. [46]
  E. Wang, R. Han, M. Wu, et al., Chin. Chem. Lett. 35 (2024) 108361. doi: 10.1016/j.cclet.2023.108361
1. [1]
  Xing Tian , Di Wu , Wanheng Wei , Guifu Dai , Zhanxian Li , Benhua Wang , Mingming Yu . A lipid droplets-targetable fluorescent probe for polarity detection in cells of iron death, inflammation and fatty liver tissue. Chinese Chemical Letters, 2024, 35(6): 108912-. doi: 10.1016/j.cclet.2023.108912
2. [2]
  Ling Tang , Yan Wan , Yangming Lin . Lowering the kinetic barrier via enhancing electrophilicity of surface oxygen to boost acidic oxygen evolution reaction. Chinese Journal of Structural Chemistry, 2024, 43(11): 100345-100345. doi: 10.1016/j.cjsc.2024.100345
3. [3]
  Yong-Dan Zhao , Yidan Wang , Rongrong Wang , Lina Chen , Hengtong Zuo , Xi Wang , Jihong Qiang , Geng Wang , Qingxia Li , Canqi Ping , Shuqiu Zhang , Hao Wang . Reversing artemisinin resistance by leveraging thermo-responsive nanoplatform to downregulating GSH. Chinese Chemical Letters, 2024, 35(6): 108929-. doi: 10.1016/j.cclet.2023.108929
4. [4]
  Lei Shen , Hongmei Liu , Ming Jin , Jinchao Zhang , Caixia Yin , Shuxiang Wang , Yutao Yang . “Three-in-one” strategy of trifluoromethyl regulated blood-brain barrier permeable fluorescent probe for peroxynitrite and antiepileptic evaluation of edaravone. Chinese Chemical Letters, 2024, 35(10): 109572-. doi: 10.1016/j.cclet.2024.109572
5. [5]
  Chun-Yun Ding , Ru-Yuan Zhang , Yu-Wu Zhong , Jiannian Yao . Binary and heterostructured microplates of iridium and ruthenium complexes: Preparation, characterization, and thermo-responsive emission. Chinese Journal of Structural Chemistry, 2024, 43(10): 100393-100393. doi: 10.1016/j.cjsc.2023.100393
6. [6]
  Xiaoliu Liang , Chunliu Huang , Hui Liu , Hu Chen , Jiabao Shou , Hongwei Cheng , Gang Liu . Natural hydrogel dressings in wound care: Design, advances, and perspectives. Chinese Chemical Letters, 2024, 35(10): 109442-. doi: 10.1016/j.cclet.2023.109442
7. [7]
  Jianye Kang , Xinyu Yang , Xuhao Yang , Jiahui Sun , Yuhang Liu , Shutao Wang , Wenlong Song . Carbon dots-enhanced pH-responsive lubricating hydrogel based on reversible dynamic covalent bondings. Chinese Chemical Letters, 2024, 35(5): 109297-. doi: 10.1016/j.cclet.2023.109297
8. [8]
  Ningyue Xu , Jun Wang , Lei Liu , Changyang Gong . Injectable hydrogel-based drug delivery systems for enhancing the efficacy of radiation therapy: A review of recent advances. Chinese Chemical Letters, 2024, 35(8): 109225-. doi: 10.1016/j.cclet.2023.109225
9. [9]
  Xin Li , Xuan Ding , Junkun Zhou , Hui Shi , Zhenxi Dai , Jiayi Liu , Yongcun Ma , Penghui Shao , Liming Yang , Xubiao Luo . Utilizing synergistic effects of bifunctional polymer hydrogel PAM-PAMPS for selective capture of Pb(Ⅱ) from wastewater. Chinese Chemical Letters, 2024, 35(7): 109158-. doi: 10.1016/j.cclet.2023.109158
10. [10]
  Xinyue Lan , Junguang Liang , Churan Wen , Xiaolong Quan , Huimin Lin , Qinqin Xu , Peixian Chen , Guangyu Yao , Dan Zhou , Meng Yu . Photo-manipulated polyunsaturated fatty acid-doped liposomal hydrogel for flexible photoimmunotherapy. Chinese Chemical Letters, 2024, 35(4): 108616-. doi: 10.1016/j.cclet.2023.108616
11. [11]
  Ruikui YAN , Xiaoli CHEN , Miao CAI , Jing REN , Huali CUI , Hua YANG , Jijiang WANG . Design, synthesis, and fluorescence sensing performance of highly sensitive and multi-response lanthanide metal-organic frameworks. Chinese Journal of Inorganic Chemistry, 2024, 40(4): 834-848. doi: 10.11862/CJIC.20230301
12. [12]
  Guorong Li , Yijing Wu , Chao Zhong , Yixin Yang , Zian Lin . Predesigned covalent organic framework with sulfur coordination: Anchoring Au nanoparticles for sensitive colorimetric detection of Hg(Ⅱ). Chinese Chemical Letters, 2024, 35(5): 108904-. doi: 10.1016/j.cclet.2023.108904
13. [13]
  Xiangqian Cao , Chenkai Yang , Xiaodong Zhu , Mengxin Zhao , Yilin Yan , Zhengnan Huang , Jinming Cai , Jingming Zhuang , Shengzhou Li , Wei Li , Bing Shen . Synergistic enhancement of chemotherapy for bladder cancer by photothermal dual-sensitive nanosystem with gold nanoparticles and PNIPAM. Chinese Chemical Letters, 2024, 35(8): 109199-. doi: 10.1016/j.cclet.2023.109199
14. [14]
  Xin Dong , Jing Liang , Zhijin Xu , Huajie Wu , Lei Wang , Shihai You , Junhua Luo , Lina Li . Exploring centimeter-sized crystals of bismuth-iodide perovskite toward highly sensitive X-ray detection. Chinese Chemical Letters, 2024, 35(6): 108708-. doi: 10.1016/j.cclet.2023.108708
15. [15]
  Linfang Wang , Jing Liu , Minghao Ren , Wei Guo . A highly sensitive fluorescent HClO probe for discrimination between cancerous and normal cells/tissues. Chinese Chemical Letters, 2024, 35(6): 108945-. doi: 10.1016/j.cclet.2023.108945
16. [16]
  Ting-Ting Huang , Jin-Fa Chen , Juan Liu , Tai-Bao Wei , Hong Yao , Bingbing Shi , Qi Lin . A novel fused bi-macrocyclic host for sensitive detection of Cr₂O₇²⁻ based on enrichment effect. Chinese Chemical Letters, 2024, 35(7): 109281-. doi: 10.1016/j.cclet.2023.109281
17. [17]
  Lan Yang , Yu Li , Mou Jiang , Rui Zhou , Hengjiang Cong , Minghui Yang , Lei Zhang , Shenhui Li , Yunhuang Yang , Maili Liu , Xin Zhou , Zhong-Xing Jiang , Shizhen Chen . Fluorinated [2]rotaxanes as sensitive ¹⁹F MRI agents: Threading for higher sensitivity. Chinese Chemical Letters, 2024, 35(10): 109512-. doi: 10.1016/j.cclet.2024.109512
18. [18]
  Ningning Gao , Yue Zhang , Zhenhao Yang , Lijing Xu , Kongyin Zhao , Qingping Xin , Junkui Gao , Junjun Shi , Jin Zhong , Huiguo Wang . Ba²⁺/Ca²⁺ co-crosslinked alginate hydrogel filtration membrane with high strength, high flux and stability for dye/salt separation. Chinese Chemical Letters, 2024, 35(5): 108820-. doi: 10.1016/j.cclet.2023.108820
19. [19]
  Shuangying Li , Qingxiang Zhou , Zhi Li , Menghua Liu , Yanhui Li . Sensitive measurement of silver ions in environmental water samples integrating magnetic ion-imprinted solid phase extraction and carbon dot fluorescent sensor. Chinese Chemical Letters, 2024, 35(5): 108693-. doi: 10.1016/j.cclet.2023.108693
20. [20]
  Simin Wei , Yaqing Yang , Junjie Li , Jialin Wang , Jinlu Tang , Ningning Wang , Zhaohui Li . The Mn/Yb/Er triple-doped CeO₂ nanozyme with enhanced oxidase-like activity for highly sensitive ratiometric detection of nitrite. Chinese Chemical Letters, 2024, 35(6): 109114-. doi: 10.1016/j.cclet.2023.109114

Get Citation

PDF

XML

Metrics

PDF Downloads(1)
Abstract views(156)
HTML views(5)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142