Hydrogen peroxide responsive covalent cyclodextrin framework for targeted therapy of inflammatory bowel disease

Chenxi Huang; Jian Xu; Jing Li; Siyu He; Huipeng Xu; Xiaohong Ren; Vikramjeet Singh; Li Wu; Jiwen Zhang

doi:10.1016/j.carbpol.2022.119252

Hydrogen peroxide responsive covalent cyclodextrin framework for targeted therapy of inflammatory bowel disease

Carbohydr Polym. 2022 Jun 1:285:119252. doi: 10.1016/j.carbpol.2022.119252. Epub 2022 Feb 12.

Authors

Chenxi Huang¹, Jian Xu¹, Jing Li¹, Siyu He¹, Huipeng Xu¹, Xiaohong Ren², Vikramjeet Singh³, Li Wu⁴, Jiwen Zhang⁵

Affiliations

¹ Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China.
² Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China.
³ Nanoengineered Systems Laboratory, UCL Mechanical Engineering, University College London, London WC1E 7JE, United Kingdom.
⁴ Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China; Anhui Province Key Laboratory of Pharmaceutical Technology and Application, Anhui University of Chinese Medicine, Hefei 230012, China; NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients, National Institutes for Food and Drug Control, Beijing 100050, China.. Electronic address: wuli@simm.ac.cn.
⁵ Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China; Anhui Province Key Laboratory of Pharmaceutical Technology and Application, Anhui University of Chinese Medicine, Hefei 230012, China; NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients, National Institutes for Food and Drug Control, Beijing 100050, China.. Electronic address: jwzhang@simm.ac.cn.

PMID: 35287866
DOI: 10.1016/j.carbpol.2022.119252

Abstract

The incidence and prevalence of inflammatory bowel disease (IBD) are steadily rising worldwide, where the pathogenesis and progression are intrinsically connected to oxidative stress and irregular high levels of reactive oxygen species. To achieve effective therapy for IBD, using hydrogen peroxide (H₂O₂)-activatable antioxidant prodrug (BRAP) as a linker to crosslink cyclodextrin metal-organic framework, a novel H₂O₂ responsive covalent cyclodextrin framework (defined as BCOF) was formulated. BCOF featured excellent ROS-responsive hydrolysis and therapeutic p-hydroxybenzyl alcohol released in a H₂O₂ concentration dependent manner in vitro. Furthermore, BCOF demonstrated 5 times greater retention in the inflamed colon compared to the normal colon in vivo following oral administration. Most importantly, BCOF improved the viability of RAW264.7 cells from H₂O₂-induced damage in vitro and alleviated the deterioration of IBD with reduced symptoms of inflammation in vivo. In conclusion, our findings suggest that BCOF deserve further consideration as a potential therapeutic nanomedicine for IBD treatment.

Keywords: Covalent cyclodextrin framework; H(2)O(2) responsive; Inflammatory bowel disease.

MeSH terms

Colitis* / drug therapy
Cyclodextrins*
Humans
Hydrogen Peroxide
Inflammatory Bowel Diseases* / drug therapy
Inflammatory Bowel Diseases* / pathology
Oxidative Stress
Reactive Oxygen Species

Substances

Cyclodextrins
Reactive Oxygen Species
Hydrogen Peroxide