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      Budesonide loaded nanoparticles with pH-sensitive coating for improved mucosal targeting in mouse models of inflammatory bowel diseases.

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          Abstract

          The purpose of this study was to investigate the therapeutic potential of budesonide loaded nanocarriers for the treatment of inflammatory bowel disease (IBD). First, budesonide was encapsulated in poly(lactic-co-glycolic) acid (PLGA) nanoparticles by an oil in water (O/W) emulsion technique. A second batch of the same nanoparticles was additionally coated with a pH-sensitive methyl-methacrylate-copolymer. The particle sizes of the plain and the coated PLGA were 200±10.1nm and ~240±14.7nm, respectively. As could be shown in vitro, the pH-sensitive coating prevented premature drug release at acidic pH and only releases the drug at neutral to slightly alkaline pH. The efficacy of both coated and plain nanoparticle formulations was assessed in different acute and chronic colitis mouse models, also in comparison to an aqueous solution of the drug. The dose was always the same (0.168mg/kg). It was found that delivery by coated PLGA nanoparticles alleviated the induced colitis significantly better than by plain PLGA particles, which was already more effective than treatment with the same dose of the free drug. These data further corroborate the potential of polymeric nanocarriers for targeted drug delivery to the inflamed intestinal mucosa, and that this concept can still be further improved regarding the oral route of administration by implementing pH-dependent drug release characteristics.

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          Author and article information

          Journal
          J Control Release
          Journal of controlled release : official journal of the Controlled Release Society
          1873-4995
          0168-3659
          Jun 10 2014
          : 183
          Affiliations
          [1 ] Biopharmaceutics and Pharmaceutical Technology, Campus A 4 1, Saarland University, 66123 Saarbrücken, Germany.
          [2 ] Medical Clinic 1, University Hospital Erlangen, 91052 Erlangen, Germany.
          [3 ] Department of Drug Delivery (DDEL), Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, Campus A 4 1, 66123 Saarbrücken, Germany.
          [4 ] Biopharmaceutics and Pharmaceutical Technology, Campus A 4 1, Saarland University, 66123 Saarbrücken, Germany; Department of Drug Delivery (DDEL), Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, Campus A 4 1, 66123 Saarbrücken, Germany.
          [5 ] Biopharmaceutics and Pharmaceutical Technology, Campus A 4 1, Saarland University, 66123 Saarbrücken, Germany; Department of Drug Delivery (DDEL), Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, Campus A 4 1, 66123 Saarbrücken, Germany. Electronic address: lehr@mx.uni-saarland.de.
          Article
          S0168-3659(14)00184-9
          10.1016/j.jconrel.2014.03.039
          24685705
          9cd20764-b09e-4407-af73-b88b53260544
          Copyright © 2014 Elsevier B.V. All rights reserved.
          History

          Colitis,Cytokines,DSS,Mini-endoscopy,Oxazolone,TNBS
          Colitis, Cytokines, DSS, Mini-endoscopy, Oxazolone, TNBS

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