2. Academic Validation
  3. A self-assembled, ROS-responsive Janus-prodrug for targeted therapy of inflammatory bowel disease

A self-assembled, ROS-responsive Janus-prodrug for targeted therapy of inflammatory bowel disease

  • J Control Release. 2019 Dec 28;316:66-78. doi: 10.1016/j.jconrel.2019.10.054.
Shanshan Li 1,  Aiqing Xie 1,  Hui Li 2,  Xiang Zou 3,  Qixiong Zhang 4
Affiliations

Affiliations

  • 1 College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, China.
  • 2 College of Chemical Engineering, Sichuan University, Chengdu, 610065, China.
  • 3 College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, China. Electronic address: [email protected].
  • 4 College of Pharmacy, Third Military Medical University, Chongqing, 400038, China. Electronic address: [email protected].
PMID: 31682913 DOI: 10.1016/j.jconrel.2019.10.054
Abstract

A self-assembled and oxidation-degradable Janus-prodrug, termed as Bud-ATK-Tem (B-ATK-T), was fabricated by ROS-responsive aromatized thioketal (ATK) linked anti-inflammatory drug budesonide (Bud) and antioxidant tempol (Tem). Benefiting from the hydrophobic interactions and π-π stacking interactions of ATK, prodrug B-ATK-T could self-assemble into nanoparticles (NP) in water containing lecithin and DSPE-PEG2K. The morphology of B-ATK-T NP (approximate 100-120nm) was confirmed to be regular spherical by transmission electron microscope. B-ATK-T NP was endowed high drug loading content with 41.23% for Bud and 15.55% for Tem. The rapid drug release from B-ATK-T NP proceeded in an extensive Reactive Oxygen Species (ROS)-dependent manner. More than 98% of Bud and Tem in B-ATK-T NP could release in the mimic inflammation microenvironment or phorbol-12-myristate-13-acetate (PMA)-stimulated macrophages within short time. The release of drugs in a simultaneous and proportional manner ensures that B-ATK-T NP can increase the combined efficacy of anti-inflammation and anti-oxidation. It is worth noting that B-ATK-T NP could be passively accumulated and dramatically increasing the maximum drugs concentration in the inflamed colon of mice with inflammatory bowel disease (IBD) by oral route, and avoiding potential systemic side effects. B-ATK-T NP could not only relieve colitis via inhibiting the expression of oxidative and proinflammatory mediators more than combination of free drugs, but also significantly reduce colitis-caused death. Taken together, the self-assembled, Janus-prodrug B-ATK-T NP is a promising candidate therapies for IBD, even for other inflammatory diseases.

Keywords

Inflammatory bowel disease; Janus-prodrug; ROS-responsive; Self-assembled; Site-specific therapy.

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