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Theranostics 2017; 7(15):3653-3666. doi:10.7150/thno.18183 This issue Cite

Research Paper

Dexamethasone-loaded Polymeric Nanoconstructs for Monitoring and Treating Inflammatory Bowel Disease

Aeju Lee^1,2, Claudia De Mei¹, Miguel Fereira¹, Roberto Marotta¹, Hong Yeol Yoon³, Kwangmeyung Kim³, Ick Chan Kwon³, Paolo Decuzzi^1✉

1. Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, Genova, Italy
2. International Research Organization for Advanced Science and Technology (IROAST) and Magnesium Research Center (MRC), Kumamoto University, Japan
3. Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea

✉ Corresponding author: Paolo Decuzzi, PhD. Phone: +39 010 71781 941, Fax: +39 010 71781 228, E-mail: Paolo.Decuzziit

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.

Keywords: nanoparticles, chronic inflammation, immune cells

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