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 fac-tors.The application of curcumin(Cur),an acknowledged anti-UC phytochemical compound,for UC ther-apy 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 par-ticle 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.

Chen Zhang;Jiaxin Li;Meng Xiao;Di Wang;Yan Qu;Liang Zou;Chuan Zheng;Jinming Zhang

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

中国化学快报（英文版）

[1]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].中国化学快报（英文版）,2022(11):4924-4929

mucoadhesive,multitudinous,DDSs,mucoadhesion

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