title: A comparative study of curcumin-loaded lipid-based nanocarriers in the treatment of inflammatory bowel disease.
abstract: Selective drug delivery to inflamed tissues is of widespread interest for the treatment of inflammatory bowel disease (IBD). Because a lack of physiological lipids has been described in patients suffering IBD, and some lipids present immunomodulatory properties, we hypothesize that the combination of lipids and anti-inflammatory drugs together within a nanocarrier may be a valuable strategy for overcoming IBD. In the present study, we investigated and compared the in vitro and in vivo efficacy of three lipid-based nanocarriers containing curcumin (CC) as an anti-inflammatory drug for treating IBD in a murine DSS-induced colitis model. These nanocarriers included self-nanoemulsifying drug delivery systems (SNEDDS), nanostructured lipid carriers (NLC) and lipid core-shell protamine nanocapsules (NC). In vitro, a 30-fold higher CC permeability across Caco-2 cell monolayers was obtained using NC compared to SNEDDS (NC>SNEDDS>NLC and CC suspension). The CC SNEDDS and CC NLC but not the CC NC or CC suspension significantly reduced TNF-α secretion by LPS-activated macrophages (J774 cells). In vivo, only CC NLC were able to significantly decrease neutrophil infiltration and TNF-α secretion and, thus, colonic inflammation. Our results show that a higher CC permeability does not correlate with a higher efficacy in IBD treatment, which suggests that lipidic nanocarriers exhibiting increased CC retention at the intestinal site, rather than increased CC permeability are efficient treatments of IBD.
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; University of Kinshasa, Faculty of Pharmaceutical Sciences, Pharmaceutics and Phytopharmaceutical Drug Development Research Group, 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: Régis
authors.initials: R
authors.lastname: Coco
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Health Research Institute of Santiago de Compostela (IDIS), Dept. Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Santiago de Compostela, 15782 Campus Vida, Santiago de Compostela, Spain; Nano-oncologicals lab, Translational Medical Oncology, Health Research Institute of Santiago de Compostela (IDIS), Clinical University Hospital of Santiago de Compostela (CHUS), Santiago de Compostela, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Reimondez-Troitiño
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Bioanalysis and Pharmacology of Bioactive Lipids Research Group, 1200 Brussels, Belgium.
authors.forename: Mireille
authors.initials: M
authors.lastname: Alhouayek
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Bioanalysis and Pharmacology of Bioactive Lipids Research Group, 1200 Brussels, Belgium.
authors.forename: Giulio G
authors.initials: GG
authors.lastname: Muccioli
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Health Research Institute of Santiago de Compostela (IDIS), Dept. Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Santiago de Compostela, 15782 Campus Vida, Santiago de Compostela, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Alonso
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Health Research Institute of Santiago de Compostela (IDIS), Dept. Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Santiago de Compostela, 15782 Campus Vida, Santiago de Compostela, Spain.
authors.forename: Noemi
authors.initials: N
authors.lastname: Csaba
authors.affiliation: Nano-oncologicals lab, Translational Medical Oncology, Health Research Institute of Santiago de Compostela (IDIS), Clinical University Hospital of Santiago de Compostela (CHUS), Santiago de Compostela, Spain.
authors.forename: María
authors.initials: M
authors.lastname: de la Fuente
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; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D018938:Caco-2 Cells; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D016264:Dextran Sulfate; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D008055:Lipids; D014409:Tumor Necrosis Factor-alpha; D016264:Dextran Sulfate; D003474:Curcumin
keywords: Curcumin; IBD; Lipids; NLC; Nanocapsules; SNEDDS