Dexamethasone-loaded polymeric nanoconstructs for monitoring and treating inflammatory bowel disease

Aeju Lee, Claudia De Mei, Miguel Fereira, Roberto Marotta, Hong Yeol Yoon, Kwang Meyung Kim, Ick Chan Kwon, Paolo Decuzzi

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8 Citations (Scopus)

Abstract

Corticosteroids, such as dexamethasone (DEX), are the mainstays for the treatment of moderate to severe inflammatory bowel disease (IBD). However, their relatively poor bioavailability and lack of specificity is often the origin of short and long-term adverse effects. Here, spherical polymeric nanoconstructs (SPNs) encapsulating dexamethasone are proposed for the systemic treatment of IBD. In a mouse model of colitis, the accumulation of SPNs within the inflamed intestine is firstly assessed using near infra-red fluorescent (NIRF) imaging at different stages of the disease – 5, 7 and 10 days of Dextran Sulfate Sodium (DSS) administration. Then, the efficacy of DEX-SPNs is tested in vitro over macrophages and in vivo by monitoring the animal weight, food and water intake; expression of inflammatory cytokines (TNF-α, IL-1β, IL-6); intestinal density of macrophages; rectal bleeding and histological scoring. 150 nm DEX-SPNs are shown to deposit within the hyper-permeable inflamed intestine in a disease severity-dependent fashion. DEX-SPNs exposed to LPS-stimulated RAW 264.7 cells reduce the expression of inflammatory cytokines as rapidly as free DEX. In DSS-administered mice, DEX-SPNs treatments improve weight loss, reduce the macrophage infiltration, expression of inflammatory cytokines, rectal bleeding and histological scoring, as compared to free DEX. Moreover, DEX-SPNs exert a strong systemic anti-inflammatory effect and facilitate animal recovery. This work confirms the benefits of using sufficiently small nanoconstructs for targeting inflamed, hyper-permeable tissues and efficiently delivering high doses of corticosteroids for the treatment of intestinal and systemic inflammation.

Original languageEnglish
Pages (from-to)3653-3666
Number of pages14
JournalTheranostics
Volume7
Issue number15
DOIs
Publication statusPublished - 2017 Jan 1
Externally publishedYes

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Keywords

  • Chronic inflammation
  • Immune cells
  • Nanoparticles

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

Cite this

Lee, A., De Mei, C., Fereira, M., Marotta, R., Yoon, H. Y., Kim, K. M., Kwon, I. C., & Decuzzi, P. (2017). Dexamethasone-loaded polymeric nanoconstructs for monitoring and treating inflammatory bowel disease. Theranostics, 7(15), 3653-3666. https://doi.org/10.7150/thno.18183