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Pharmaceutics
Volume 18
Issue 5
10.3390/pharmaceutics18050602
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Article

Disulfide Cross-Linked Thiolated Chitosan/Oxidized Dextran–Oleylamine Micelle–Hydrogel System with pH/ROS Dual-Responsive Cascade Drug Release for Integrated Colon Targeting and Mucosal Repair in Inflammatory Bowel Disease

by
Jiangtao He
1,†,
Chunyu Gan
1,†,
Tongxia Chi
1,
Jia Liu
1,
Tuya Bai
1,2,
Xin Wu
3,
Guodong Liang
1,
Ruijuan Li
1,* and
Yuheng Ma
1,*
1
College of Pharmacy, Inner Mongolia Medical University, Hohhot 010110, China
2
Inner Mongolia Autonomous Region Engineering Research Center of New Pharmaceutical Screening, Inner Mongolia Medical University, Hohhot 010110, China
3
Shanghai Wei Er Lab, No. 358, Tian Chen Road, Qingpu District, Shanghai 201707, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Pharmaceutics 2026, 18(5), 602; https://doi.org/10.3390/pharmaceutics18050602 (registering DOI)
Submission received: 14 April 2026 / Revised: 12 May 2026 / Accepted: 12 May 2026 / Published: 14 May 2026
(This article belongs to the Section Drug Delivery and Controlled Release)
Versions Notes

Abstract

Background: Oral colon-targeted delivery for inflammatory bowel disease (IBD) faces significant challenges, including limited gastrointestinal stability, premature drug release, and insufficient mucosal retention. Methods: To address these limitations, a mucoadhesive polysaccharide-based composite hydrogel incorporating prednisolone-loaded polymeric micelles was developed to enhance colonic delivery and promote mucosal repair. Amphiphilic oxidized dextran–oleylamine (ODEX-OA) copolymers were synthesized to self-assemble into prednisolone-loaded micelles. These micelles were subsequently embedded within a thiolated chitosan (CSSH) hydrogel through a Schiff base reaction, yielding the ODEX-OA-Pred-CSSH composite. The resulting system was comprehensively characterized for particle size, mucoadhesion, degradation, and pH/ROS dual-responsive drug release. Its colon-targeting capability and therapeutic efficacy were subsequently assessed in a dextran sulfate sodium (DSS)-induced colitis mouse model. Results: In vitro, the composite hydrogel demonstrated nanoscale micellar size, enhanced drug release kinetics under simulated inflammatory colonic conditions, and prolonged colonic retention for up to 24 h following oral administration. In vivo, studies confirmed that ODEX-OA-Pred-CSSH significantly alleviated colitis, evidenced by a reduced disease activity index, diminished pro-inflammatory cytokine levels, restored colon length, decreased spleen index, and improved histological mucosal repair. Conclusions: These findings collectively suggest that this mucoadhesive micelle–hydrogel composite represents a promising and effective oral colon-targeted platform for the treatment of IBD.
Keywords: inflammatory bowel disease; oral colon-targeted delivery; polymeric micelles; mucoadhesive hydrogel; mucosal repair inflammatory bowel disease; oral colon-targeted delivery; polymeric micelles; mucoadhesive hydrogel; mucosal repair

Share and Cite

MDPI and ACS Style

He, J.; Gan, C.; Chi, T.; Liu, J.; Bai, T.; Wu, X.; Liang, G.; Li, R.; Ma, Y. Disulfide Cross-Linked Thiolated Chitosan/Oxidized Dextran–Oleylamine Micelle–Hydrogel System with pH/ROS Dual-Responsive Cascade Drug Release for Integrated Colon Targeting and Mucosal Repair in Inflammatory Bowel Disease. Pharmaceutics 2026, 18, 602. https://doi.org/10.3390/pharmaceutics18050602

AMA Style

He J, Gan C, Chi T, Liu J, Bai T, Wu X, Liang G, Li R, Ma Y. Disulfide Cross-Linked Thiolated Chitosan/Oxidized Dextran–Oleylamine Micelle–Hydrogel System with pH/ROS Dual-Responsive Cascade Drug Release for Integrated Colon Targeting and Mucosal Repair in Inflammatory Bowel Disease. Pharmaceutics. 2026; 18(5):602. https://doi.org/10.3390/pharmaceutics18050602

Chicago/Turabian Style

He, Jiangtao, Chunyu Gan, Tongxia Chi, Jia Liu, Tuya Bai, Xin Wu, Guodong Liang, Ruijuan Li, and Yuheng Ma. 2026. "Disulfide Cross-Linked Thiolated Chitosan/Oxidized Dextran–Oleylamine Micelle–Hydrogel System with pH/ROS Dual-Responsive Cascade Drug Release for Integrated Colon Targeting and Mucosal Repair in Inflammatory Bowel Disease" Pharmaceutics 18, no. 5: 602. https://doi.org/10.3390/pharmaceutics18050602

APA Style

He, J., Gan, C., Chi, T., Liu, J., Bai, T., Wu, X., Liang, G., Li, R., & Ma, Y. (2026). Disulfide Cross-Linked Thiolated Chitosan/Oxidized Dextran–Oleylamine Micelle–Hydrogel System with pH/ROS Dual-Responsive Cascade Drug Release for Integrated Colon Targeting and Mucosal Repair in Inflammatory Bowel Disease. Pharmaceutics, 18(5), 602. https://doi.org/10.3390/pharmaceutics18050602

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