title: pH-sensitive nanoparticles for colonic delivery of curcumin in inflammatory bowel disease.
abstract: Nano-scaled particles have been found to preferentially accumulate in inflamed regions. Local delivery of anti-inflammatory drugs loaded in nanoparticles to the inflamed colonic site is of great interest for inflammatory bowel disease (IBD) treatment. Curcumin (CC) is an anti-inflammatory local agent, which presents poor ADME properties. Hence, we evaluated, both in vitro and in vivo, the local delivery of CC using pH-sensitive polymeric nanoparticles (NPs) combining both poly(lactide-co-glycolide) acid (PLGA) and a polymethacrylate polymer (Eudragit(®) S100). CC-NPs significantly enhanced CC permeation across Caco-2 cell monolayers when compared to CC in suspension. CC-NPs significantly reduced TNF-α secretion by LPS-activated macrophages (J774 cells). In vivo, CC-NPs significantly decreased neutrophil infiltration and TNF-α secretion while maintaining the colonic structure similar to the control group in a murine DSS-induced colitis model. Our results support the use of nanoparticles made of PLGA and Eudragit(®) S100 combination for CC delivery in IBD treatment.
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium.
authors.forename: Ana
authors.initials: A
authors.lastname: Beloqui
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium.
authors.forename: Régis
authors.initials: R
authors.lastname: Coco
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium; University of Kinshasa, Faculty of Pharmaceutical Sciences, Laboratoire de Pharmacie galénique, BP 212 Kinshasa XI,Democratic Republic of the Congo.
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Memvanga
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Ucakar
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: des Rieux
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium. Electronic address: veronique.preat@uclouvain.be.
authors.forename: Véronique
authors.initials: V
authors.lastname: Préat
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry; D018938:Caco-2 Cells; D002460:Cell Line; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D019344:Lactic Acid / Q000737:chemistry; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011109:Polymethacrylic Acids / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D011109:Polymethacrylic Acids; D014409:Tumor Necrosis Factor-alpha; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C038300:methylmethacrylate-methacrylic acid copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D016264:Dextran Sulfate; D003474:Curcumin
keywords: Curcumin; Eudragit(®); Inflammatory bowel disease; Nanoparticles; PLGA; pH-sensitive