Lee, Aeju De Mei, Claudia Fereira, Miguel Marotta, Roberto Yoon, Hong Yeol Kim, Kwangmeyung Kwon, Ick Chan Decuzzi, Paolo 2024-01-20T01:01:47Z 2024-01-20T01:01:47Z 2021-09-05 2017-08 1838-7640 https://pubs.kist.re.kr/handle/201004/122478 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-alpha, IL-1 beta, 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-alpha dministered 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. English IVYSPRING INT PUBL CROHNS-DISEASE INTESTINAL PERMEABILITY DRUG-DELIVERY THERAPY NANOCARRIERS PATHOGENESIS CELLS RISK TNF IBD Dexamethasone-loaded Polymeric Nanoconstructs for Monitoring and Treating Inflammatory Bowel Disease Article 10.7150/thno.18183 1 THERANOSTICS, v.7, no.15, pp.3653 - 3666 THERANOSTICS 7 15 3653 3666 scie scopus 000408444200004 2-s2.0-85028515344 Medicine, Research & Experimental Research & Experimental Medicine Article CROHNS-DISEASE INTESTINAL PERMEABILITY DRUG-DELIVERY THERAPY NANOCARRIERS PATHOGENESIS CELLS RISK TNF IBD nanoparticles chronic inflammation immune cells