Cargando…
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 az...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4509535/ https://www.ncbi.nlm.nih.gov/pubmed/26213469 http://dx.doi.org/10.2147/IJN.S87816 |
_version_ | 1782382046990041088 |
---|---|
author | Naeem, Muhammad Cao, Jiafu Choi, Moonjeong Kim, Woo Seong Moon, Hyung Ryong Lee, Bok Luel Kim, Min-Soo Jung, Yunjin Yoo, Jin-Wook |
author_facet | Naeem, Muhammad Cao, Jiafu Choi, Moonjeong Kim, Woo Seong Moon, Hyung Ryong Lee, Bok Luel Kim, Min-Soo Jung, Yunjin Yoo, Jin-Wook |
author_sort | Naeem, Muhammad |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4509535 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-45095352015-07-24 Enhanced therapeutic efficacy of budesonide in experimental colitis with enzyme/pH dual-sensitive polymeric nanoparticles Naeem, Muhammad Cao, Jiafu Choi, Moonjeong Kim, Woo Seong Moon, Hyung Ryong Lee, Bok Luel Kim, Min-Soo Jung, Yunjin Yoo, Jin-Wook Int J Nanomedicine Original Research 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. Dove Medical Press 2015-07-16 /pmc/articles/PMC4509535/ /pubmed/26213469 http://dx.doi.org/10.2147/IJN.S87816 Text en © 2015 Naeem et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Naeem, Muhammad Cao, Jiafu Choi, Moonjeong Kim, Woo Seong Moon, Hyung Ryong Lee, Bok Luel Kim, Min-Soo Jung, Yunjin Yoo, Jin-Wook Enhanced therapeutic efficacy of budesonide in experimental colitis with enzyme/pH dual-sensitive polymeric nanoparticles |
title | Enhanced therapeutic efficacy of budesonide in experimental colitis with enzyme/pH dual-sensitive polymeric nanoparticles |
title_full | Enhanced therapeutic efficacy of budesonide in experimental colitis with enzyme/pH dual-sensitive polymeric nanoparticles |
title_fullStr | Enhanced therapeutic efficacy of budesonide in experimental colitis with enzyme/pH dual-sensitive polymeric nanoparticles |
title_full_unstemmed | Enhanced therapeutic efficacy of budesonide in experimental colitis with enzyme/pH dual-sensitive polymeric nanoparticles |
title_short | Enhanced therapeutic efficacy of budesonide in experimental colitis with enzyme/pH dual-sensitive polymeric nanoparticles |
title_sort | enhanced therapeutic efficacy of budesonide in experimental colitis with enzyme/ph dual-sensitive polymeric nanoparticles |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4509535/ https://www.ncbi.nlm.nih.gov/pubmed/26213469 http://dx.doi.org/10.2147/IJN.S87816 |
work_keys_str_mv | AT naeemmuhammad enhancedtherapeuticefficacyofbudesonideinexperimentalcolitiswithenzymephdualsensitivepolymericnanoparticles AT caojiafu enhancedtherapeuticefficacyofbudesonideinexperimentalcolitiswithenzymephdualsensitivepolymericnanoparticles AT choimoonjeong enhancedtherapeuticefficacyofbudesonideinexperimentalcolitiswithenzymephdualsensitivepolymericnanoparticles AT kimwooseong enhancedtherapeuticefficacyofbudesonideinexperimentalcolitiswithenzymephdualsensitivepolymericnanoparticles AT moonhyungryong enhancedtherapeuticefficacyofbudesonideinexperimentalcolitiswithenzymephdualsensitivepolymericnanoparticles AT leebokluel enhancedtherapeuticefficacyofbudesonideinexperimentalcolitiswithenzymephdualsensitivepolymericnanoparticles AT kimminsoo enhancedtherapeuticefficacyofbudesonideinexperimentalcolitiswithenzymephdualsensitivepolymericnanoparticles AT jungyunjin enhancedtherapeuticefficacyofbudesonideinexperimentalcolitiswithenzymephdualsensitivepolymericnanoparticles AT yoojinwook enhancedtherapeuticefficacyofbudesonideinexperimentalcolitiswithenzymephdualsensitivepolymericnanoparticles |