Oral Delivery of Transformable Bilirubin Self-assembled System for Targeted Therapy of Colitis.
Zhejie ChenYi ChenWei HaoMingju ShuiJinming ZhangHefeng ZhouChen ZhangYitao WangShengpeng WangPublished in: Advanced healthcare materials (2023)
Ulcerative colitis (UC) is a high incidence disease worldwide and clinically presents as relapsing and incurable inflammation of the colon. Bilirubin (BR), a natural antioxidant with significant anti-colitic effects, has been utilized in preclinical studies as an intestinal disease therapy. Due to their water-insolubility, the design of BR-based agents usually involves complicated chemosynthetic processes, introducing various uncertainties in BR development. After screening numerous materials, we identified that chondroitin sulfate can efficiently mediate the construction of BR self-assembled nanomedicine (BSNM) via intermolecular hydrogen bonds between dense sulfate and carboxyl of chondroitin sulfate and imino groups of BR. BSNM exhibits pH sensitivity and reactive oxygen species responsiveness, enabling targeted delivery to the colon. After oral administration, BSNM significantly inhibits colonic fibrosis and apoptosis of colon and goblet cells; it also reduces the expression of inflammatory cytokines. Moreover, BSNM maintains the normal level of zonula occludens-1 (ZO-1) and occludin to sustain the integrity of intestinal barrier, regulates the macrophage polarization from M1 to M2 type, and promotes the ecological recovery of intestinal flora. Collectively, our work provides a colon-targeted and transformable BSNM that is simple to prepare and is useful as an efficient targeted UC therapy. This article is protected by copyright. All rights reserved.
Keyphrases
- ulcerative colitis
- oxidative stress
- cell cycle arrest
- induced apoptosis
- reactive oxygen species
- cancer therapy
- multiple sclerosis
- poor prognosis
- cell death
- endoplasmic reticulum stress
- hyaluronic acid
- risk factors
- climate change
- stem cells
- risk assessment
- rheumatoid arthritis
- cell therapy
- cell proliferation
- signaling pathway