Citation: Chen Zhang, Jiaxin Li, Meng Xiao, Di Wang, Yan Qu, Liang Zou, Chuan Zheng, Jinming Zhang. Oral colon-targeted mucoadhesive micelles with enzyme-responsive controlled release of curcumin for ulcerative colitis therapy[J]. Chinese Chemical Letters, ;2022, 33(11): 4924-4929. doi: 10.1016/j.cclet.2022.03.110 shu

Oral colon-targeted mucoadhesive micelles with enzyme-responsive controlled release of curcumin for ulcerative colitis therapy

Chen Zhang ^{a, 1} ,
Jiaxin Li ^{a, 1} ,
Meng Xiao ^a ,
Di Wang ^a ,
Yan Qu ^a ,
Liang Zou ^b ,
Chuan Zheng ^{a, c, *,} ,
Jinming Zhang ^{a, *,}

a.
State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, China
b.
Key Laboratory of Coarse Cereal Processing, Ministry of Agriculture and Rural Affairs, Chengdu University, Chengdu 610106, China
c.
Oncology Teaching and Research Department, Hospital of Chengdu University of Traditional of Chinese Medicine, Chengdu 610072, China

zhengchuan@cdutcm.edu.cn

cdutcmzjm@126.com

Received Date: 9 December 2021
Revised Date: 29 March 2022
Accepted Date: 29 March 2022
Available Online: 2 April 2022

Figures(4)

Although multitudinous nanoscale drug-delivery systems (DDSs) have been recommended to improve anti-ulcerative colitis (UC) outcomes, to enhance the mucoadhesion of nanosystems on the colon and specifically release the loaded drugs in response to the colon micro-environment would be critical factors. The application of curcumin (Cur), an acknowledged anti-UC phytochemical compound, for UC therapy requires more efficient nano-carriers to improve its therapeutic outcome. Herein, we developed the colon-targeted nano-micelles with mucoadhesive effect and Azo reductase-triggered drug release profiles for Cur delivery in UC treatment. Specifically, the amphiphilic block polymer containing the Azo-reductase sensitive linkage (PEG-Azo-PLGA), and catechol-modified TPGS (Cat-TPGS) were synthesized respectively. Based on the self-assembly of the mixed polymers, Cur-micelles (142.7 ± 1.7 nm of average size, 72.36% ± 1.54% of DEE) were obtained. Interestingly, the Cur-micelles exhibited the Azo-reductase sensitive particle dissociation and drug release, the enhanced cellular uptake and the prolonged retention on colonic mucosa, mediated by the strong mucoadhesion of catechol structure. Ultimately, Cur-micelles significantly mitigated colitis symptoms and accelerated colitis repair in DSS-treated mice by regulating the intestinal flora and the levels of pro-inflammatory factors (MPO, IL-6, IL-1β, and TNF-α) related to TLR4/MyD88/NF-κB signaling pathway. This work provides an effective drug delivery strategy for anti-UC drugs by oral administration.
- Curcumin,
- Enzyme-responsive,
- Micelles,
- Mucoadhesion,
- Ulcerative colitis
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