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.
Keywords:
Curcumin; Eudragit(®); Inflammatory bowel disease; Nanoparticles; PLGA; pH-sensitive.
Copyright © 2014 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Inflammatory Agents / administration & dosage*
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Anti-Inflammatory Agents / chemistry
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Caco-2 Cells
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Cell Line
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Colitis / chemically induced
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Colitis / drug therapy*
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Colitis / metabolism
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Colitis / pathology
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Colon / metabolism
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Colon / pathology
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Curcumin / administration & dosage*
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Curcumin / chemistry
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Dextran Sulfate
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Disease Models, Animal
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Drug Carriers / administration & dosage*
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Drug Carriers / chemistry
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Female
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Humans
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Hydrogen-Ion Concentration
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Inflammatory Bowel Diseases / chemically induced
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Inflammatory Bowel Diseases / drug therapy
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Inflammatory Bowel Diseases / metabolism
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Inflammatory Bowel Diseases / pathology
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Lactic Acid / chemistry
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Macrophages / drug effects
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Macrophages / metabolism
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Mice, Inbred C57BL
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Nanoparticles / administration & dosage*
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Nanoparticles / chemistry
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Neutrophils / drug effects
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Neutrophils / metabolism
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Polyglycolic Acid / chemistry
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Polylactic Acid-Polyglycolic Acid Copolymer
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Polymethacrylic Acids / chemistry
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Anti-Inflammatory Agents
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Drug Carriers
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Polymethacrylic Acids
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Tumor Necrosis Factor-alpha
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Polylactic Acid-Polyglycolic Acid Copolymer
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methylmethacrylate-methacrylic acid copolymer
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Polyglycolic Acid
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Lactic Acid
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Dextran Sulfate
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Curcumin