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Drug delivery to inflamed colon by nanoparticles: Comparison of different strategies

Coco, Régis, Plapied, Laurence, Pourcelle, Vincent, Jérôme, Christine, Brayden, David J., Schneider, Yves-Jacques, Préat, Véronique·2013·International Journal of Pharmaceutics
DOI 10.1016/j.ijpharm.2012.07.017
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Abstract

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…

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Metadata

Authors
Coco, R., Plapied, L., Pourcelle, V., Jérôme, C., Brayden, D. J., Schneider, Y.-J., & Préat, V.
Venue
International Journal of Pharmaceutics
Publisher
Elsevier BV
Published
2013-01
Volume
440
Issue
1
Pages
3-12
ISSN
0378-5173
DOI
10.1016/j.ijpharm.2012.07.017
Cited by
162
References
2
Language
en
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)

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