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Nanogels of a Succinylated Glycol Chitosan-Succinyl Prednisolone Conjugate: Release Behavior, Gastrointestinal Distribution, and Systemic Absorption
Recently, the potential of nanoparticles (NPs) in ulcerative colitis (UC) therapy has been increasingly demonstrated. Namely, anionic NPs have been found to be accumulated efficiently to the UC damaged area due to epithelial enhanced permeability and retention (eEPR) effect. Previously, a novel anio...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178247/ https://www.ncbi.nlm.nih.gov/pubmed/32235554 http://dx.doi.org/10.3390/ijms21072376 |
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author | Zhou, Haiyan Ikeuchi-Takahashi, Yuri Hattori, Yoshiyuki Onishi, Hiraku |
author_facet | Zhou, Haiyan Ikeuchi-Takahashi, Yuri Hattori, Yoshiyuki Onishi, Hiraku |
author_sort | Zhou, Haiyan |
collection | PubMed |
description | Recently, the potential of nanoparticles (NPs) in ulcerative colitis (UC) therapy has been increasingly demonstrated. Namely, anionic NPs have been found to be accumulated efficiently to the UC damaged area due to epithelial enhanced permeability and retention (eEPR) effect. Previously, a novel anionic nanogel system (NG(S)) was prepared, and evaluated for the efficacy and toxicity. In the present study, release behaviors and biodistribution were investigated in detail to elucidate the functional mechanisms. Rats with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced ulcerative colitis (UC) were used as biomodels. In vitro release was examined with or without the contents of the cecum or distal colon. Gastrointestinal distribution and plasma concentrations were investigated after the intragastric administration of 10 mg prednisolone (PD) eq./kg. At pH 1.2 and 6.8, release behaviors were slow, but controlled. Overall release was not markedly different irrespective of coexistence of intestinal contents. In in vivo studies, a large amount of PD was distributed in the lower parts of the gastrointestinal tract 6 and 12 h after administration with NG(S). PD accumulated well in the colonic parts, and prolonged release was noted. The systemic absorption of PD with NG(S) was hardly found. NG(S) concentrated the drug in the colon and showed controlled release. These behaviors were considered to lead to the previously reported good results, promotion of effectiveness and suppression of toxic side effects. |
format | Online Article Text |
id | pubmed-7178247 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-71782472020-04-28 Nanogels of a Succinylated Glycol Chitosan-Succinyl Prednisolone Conjugate: Release Behavior, Gastrointestinal Distribution, and Systemic Absorption Zhou, Haiyan Ikeuchi-Takahashi, Yuri Hattori, Yoshiyuki Onishi, Hiraku Int J Mol Sci Article Recently, the potential of nanoparticles (NPs) in ulcerative colitis (UC) therapy has been increasingly demonstrated. Namely, anionic NPs have been found to be accumulated efficiently to the UC damaged area due to epithelial enhanced permeability and retention (eEPR) effect. Previously, a novel anionic nanogel system (NG(S)) was prepared, and evaluated for the efficacy and toxicity. In the present study, release behaviors and biodistribution were investigated in detail to elucidate the functional mechanisms. Rats with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced ulcerative colitis (UC) were used as biomodels. In vitro release was examined with or without the contents of the cecum or distal colon. Gastrointestinal distribution and plasma concentrations were investigated after the intragastric administration of 10 mg prednisolone (PD) eq./kg. At pH 1.2 and 6.8, release behaviors were slow, but controlled. Overall release was not markedly different irrespective of coexistence of intestinal contents. In in vivo studies, a large amount of PD was distributed in the lower parts of the gastrointestinal tract 6 and 12 h after administration with NG(S). PD accumulated well in the colonic parts, and prolonged release was noted. The systemic absorption of PD with NG(S) was hardly found. NG(S) concentrated the drug in the colon and showed controlled release. These behaviors were considered to lead to the previously reported good results, promotion of effectiveness and suppression of toxic side effects. MDPI 2020-03-30 /pmc/articles/PMC7178247/ /pubmed/32235554 http://dx.doi.org/10.3390/ijms21072376 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zhou, Haiyan Ikeuchi-Takahashi, Yuri Hattori, Yoshiyuki Onishi, Hiraku Nanogels of a Succinylated Glycol Chitosan-Succinyl Prednisolone Conjugate: Release Behavior, Gastrointestinal Distribution, and Systemic Absorption |
title | Nanogels of a Succinylated Glycol Chitosan-Succinyl Prednisolone Conjugate: Release Behavior, Gastrointestinal Distribution, and Systemic Absorption |
title_full | Nanogels of a Succinylated Glycol Chitosan-Succinyl Prednisolone Conjugate: Release Behavior, Gastrointestinal Distribution, and Systemic Absorption |
title_fullStr | Nanogels of a Succinylated Glycol Chitosan-Succinyl Prednisolone Conjugate: Release Behavior, Gastrointestinal Distribution, and Systemic Absorption |
title_full_unstemmed | Nanogels of a Succinylated Glycol Chitosan-Succinyl Prednisolone Conjugate: Release Behavior, Gastrointestinal Distribution, and Systemic Absorption |
title_short | Nanogels of a Succinylated Glycol Chitosan-Succinyl Prednisolone Conjugate: Release Behavior, Gastrointestinal Distribution, and Systemic Absorption |
title_sort | nanogels of a succinylated glycol chitosan-succinyl prednisolone conjugate: release behavior, gastrointestinal distribution, and systemic absorption |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178247/ https://www.ncbi.nlm.nih.gov/pubmed/32235554 http://dx.doi.org/10.3390/ijms21072376 |
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