Enhanced therapeutic efficacy of budesonide in experimental colitis with enzyme/pH dual-sensitive polymeric nanoparticles

Current colon-targeted drug-delivery approaches for colitis therapy often utilize single pH-triggered systems, which are less reliable due to the variation of gut pH in individuals and in disease conditions. Herein, we prepared budesonide-loaded dual-sensitive nanoparticles using enzyme-sensitive azo-polyurethane and pH-sensitive methacrylate copolymer for the treatment of colitis. The therapeutic potential of the enzyme/pH dual-sensitive nanoparticles was evaluated using a rat colitis model and compared to single pH-triggered nanoparticles. Clinical activity scores, colon/body weight ratios, myeloperoxidase activity, and proinflammatory cytokine levels were markedly decreased by dual-sensitive nanoparticles compared to single pH-triggered nanoparticles and budesonide solution. Moreover, dual-sensitive nanoparticles accumulated selectively in inflamed segments of the colon. In addition, dual-sensitive nanoparticle plasma concentrations were lower than single pH-triggered nanoparticles, and no noticeable in vitro or in vivo toxicity was observed. Our results demonstrate that enzyme/pH dual-sensitive nanoparticles are an effective and safe colon-targeted delivery system for colitis therapy.

• Publication year

  2015

• Venue

  International Journal of Nanomedicine

• Publication date

  2015-07-16

• Fields of study

  Medicine, Materials Science

• Identifiers
  DOI 10.2147/IJN.S87816PMID 26213469PMCID 4509535
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Drug delivery strategies in the therapy of inflammatory bowel disease.

  2014cited by this paper
• Budesonide loaded nanoparticles with pH-sensitive coating for improved mucosal targeting in mouse models of inflammatory bowel diseases.

  2014cited by this paper
• Enzyme/pH dual sensitive polymeric nanoparticles for targeted drug delivery to the inflamed colon.

  2014influential reference
• Once-daily budesonide MMX in active, mild-to-moderate ulcerative colitis: results from the randomised CORE II study

  2013cited by this paper
• PNAS Plus Significance Statements

  2013cited by this paper
• Nano- and microscaled particles for drug targeting to inflamed intestinal mucosa: a first in vivo study in human patients.

  2013cited by this paper
• Chemical and cytokine features of innate immunity characterize serum and tissue profiles in inflammatory bowel disease

  2013cited by this paper
• Colonic bacterial metabolism of corticosteroids.

  2013cited by this paper
• Large intestine-targeted nanoparticle-releasing oral vaccine to control genitorectal viral infection

  2012cited by this paper
• Colon-targeted cell-permeable NFκB inhibitory peptide is orally active against experimental colitis.

  2012cited by this paper
• Nanoparticle-based clodronate delivery mitigates murine experimental colitis.

  2012cited by this paper
• Once-daily budesonide MMX® extended-release tablets induce remission in patients with mild to moderate ulcerative colitis: results from the CORE I study.

  2012cited by this paper
• pH-sensitive Eudragit nanoparticles for mucosal drug delivery.

  2011cited by this paper
• 3g mesalazine granules are superior to 9mg budesonide for achieving remission in active ulcerative colitis: a double-blind, double-dummy, randomised trial.

  2011cited by this paper
• Budesonide 9 mg is at least as effective as mesalamine 4.5 g in patients with mildly to moderately active Crohn's disease.

  2011cited by this paper
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  2010cited by this paper
• Targeted drug-delivery approaches by nanoparticulate carriers in the therapy of inflammatory diseases

  2010cited by this paper
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  2009cited by this paper
• pH-Sensitive nanospheres for colon-specific drug delivery in experimentally induced colitis rat model.

  2009cited by this paper
• Solid Lipid Budesonide Microparticles for Controlled Release Inhalation Therapy

  2009influential reference
• The transcription factor NFATc2 controls IL-6–dependent T cell activation in experimental colitis

  2008cited by this paper
• Budesonide for induction of remission in Crohn's disease.

  2008cited by this paper
• Development of pH- and time-dependent oral microparticles to optimize budesonide delivery to ileum and colon.

  2007cited by this paper
• Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases

  2007cited by this paper
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  2005cited by this paper
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  2005cited by this paper
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  2005cited by this paper
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  2000cited by this paper
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  2000cited by this paper
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