[en] For inflammatory bowel disease (IBD) treatment, local delivery of molecules loaded in nanoparticles to the inflamed colon could be a promising strategy. The aim of this study was to investigate how drug-loaded polymeric nanoparticles target the site of inflammation and to analyse the influence of different colon-specific delivery strategies. Three different polymeric nanoparticles were formulated using ovalbumin (OVA) as a model drug. pH-sensitive nanoparticles were made with Eudragit® S100. Mucoadhesive nanoparticles were created with trimethylchitosan (TMC). A mix of polymers, PLGA, PEG-PLGA and PEG-PCL, were used to obtain a sustained drug delivery. Furthermore, ligands targeting immune cells (i.e. mannose) or the inflamed colon (i.e. a specific peptide) were grafted on the PEG chain of PCL. Interaction of nanoparticles with the intestinal epithelium was explored using Caco-2 monolayers designed to mimic an inflamed epithelium and then visualized using confocal laser microscopy. TMC nanoparticles had the highest apparent permeability for OVA in the untreated model. However, in the inflamed model, there were no difference between TMC, PLGA-based and Eudragit® nanoparticles. The uptake of nanoparticles in the inflamed mouse colon was assessed in a horizontal diffusion chamber. Mannose-grafted PLGA nanoparticles showed the highest accumulation of OVA in inflamed colon. Based on these results, active targeting of macrophages and dendritic cells may be a promising approach for targeting the colon in IBD.
Research Center/Unit :
Center for Education and Research on Macromolecules (CERM)
Disciplines :
Chemistry Materials science & engineering
Author, co-author :
Coco, Régis; Université catholique de Louvain (UCL), Brussels > Louvain Drug Research Institute (LDRI) > Pharmaceutics and Drug Delivery
Plapied, Laurence; Université catholique de Louvain (UCL), Brussels > Louvain Drug Research Institute (LDRI) > Pharmaceutics and Drug Delivery
Pourcelle, Vincent; Université catholique de Louvain (UCL) > Institute of Condensed Matter and Nanosciences > Division Molecules, Solids and Reactivity
Jérôme, Christine ; Université de Liège - ULiège > Department of Chemistry > Center for Education and Research on Macromolecules (CERM)
Brayden, David J.; University College Dublin and UCD Conway Institute, Dublin > School of Veterinary Medicine
Schneider, Yves-Jacques; Université catholique de Louvain (UCL) > Institut des Sciences de la Vie
Préat, Véronique; Université catholique de Louvain (UCL), Brussels > Louvain Drug Research Institute (LDRI) > Pharmaceutics and Drug Delivery
Language :
English
Title :
Drug delivery to inflamed colon by nanoparticles: comparison of different strategies
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