title: Drug delivery to inflamed colon by nanoparticles: comparison of different strategies.
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 for targeting the colon in IBD.
authors: Université Catholique de Louvain, Louvain Drug Research Institute, Pharmaceutics and Drug Delivery, 1200 Brussels, Belgium.
authors: Régis
authors: R
authors: Coco
authors: Laurence
authors: L
authors: Plapied
authors: Vincent
authors: V
authors: Pourcelle
authors: Christine
authors: C
authors: Jérôme
authors: David J
authors: DJ
authors: Brayden
authors: Yves-Jacques
authors: YJ
authors: Schneider
authors: Véronique
authors: V
authors: Préat
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D048271:Chitosan / Q000737:chemistry; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D016207:Cytokines / Q000494:pharmacology; D016264:Dextran Sulfate; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D005027:Ethylene Oxide / Q000737:chemistry; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D007408:Intestinal Absorption; D019344:Lactic Acid / Q000737:chemistry; D007783:Lactones / Q000737:chemistry; D008358:Mannose / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010047:Ovalbumin / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011098:Polyglactin 910 / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011109:Polymethacrylic Acids / Q000737:chemistry
chemical_list: D016207:Cytokines; D004337:Drug Carriers; D007783:Lactones; C118071:N-trimethyl chitosan chloride; C400421:PLC(20)-b-PEO(44); D011109:Polymethacrylic Acids; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C038300:methylmethacrylate-methacrylic acid copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D010047:Ovalbumin; D048271:Chitosan; D016264:Dextran Sulfate; D005027:Ethylene Oxide; D008358:Mannose