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An injectable micelle-hydrogel hybrid for localized and prolonged drug delivery in the management of renal fibrosis
Localized delivery, comparing to systemic drug administration, offers a unique alternative to enhance efficacy, lower dosage, and minimize systemic tissue toxicity by releasing therapeutics locally and specifically to the site of interests. Herein, a localized drug delivery platform (“plum‒pudding”...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982499/ https://www.ncbi.nlm.nih.gov/pubmed/33777685 http://dx.doi.org/10.1016/j.apsb.2020.10.016 |
_version_ | 1783667731008061440 |
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author | Qin, Xianyan Xu, Yingying Zhou, Xu Gong, Tao Zhang, Zhi-Rong Fu, Yao |
author_facet | Qin, Xianyan Xu, Yingying Zhou, Xu Gong, Tao Zhang, Zhi-Rong Fu, Yao |
author_sort | Qin, Xianyan |
collection | PubMed |
description | Localized delivery, comparing to systemic drug administration, offers a unique alternative to enhance efficacy, lower dosage, and minimize systemic tissue toxicity by releasing therapeutics locally and specifically to the site of interests. Herein, a localized drug delivery platform (“plum‒pudding” structure) with controlled release and long-acting features is developed through an injectable hydrogel (“pudding”) crosslinked via self-assembled triblock polymeric micelles (“plum”) to help reduce renal interstitial fibrosis. This strategy achieves controlled and prolonged release of model therapeutics in the kidney for up to three weeks in mice. Following a single injection, local treatments containing either anti-inflammatory small molecule celastrol or anti-TGFβ antibody effectively minimize inflammation while alleviating fibrosis via inhibiting NF-κB signaling pathway or neutralizing TGF-β1 locally. Importantly, the micelle-hydrogel hybrid based localized therapy shows enhanced efficacy without local or systemic toxicity, which may represent a clinically relevant delivery platform in the management of renal interstitial fibrosis. |
format | Online Article Text |
id | pubmed-7982499 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-79824992021-03-25 An injectable micelle-hydrogel hybrid for localized and prolonged drug delivery in the management of renal fibrosis Qin, Xianyan Xu, Yingying Zhou, Xu Gong, Tao Zhang, Zhi-Rong Fu, Yao Acta Pharm Sin B Original Article Localized delivery, comparing to systemic drug administration, offers a unique alternative to enhance efficacy, lower dosage, and minimize systemic tissue toxicity by releasing therapeutics locally and specifically to the site of interests. Herein, a localized drug delivery platform (“plum‒pudding” structure) with controlled release and long-acting features is developed through an injectable hydrogel (“pudding”) crosslinked via self-assembled triblock polymeric micelles (“plum”) to help reduce renal interstitial fibrosis. This strategy achieves controlled and prolonged release of model therapeutics in the kidney for up to three weeks in mice. Following a single injection, local treatments containing either anti-inflammatory small molecule celastrol or anti-TGFβ antibody effectively minimize inflammation while alleviating fibrosis via inhibiting NF-κB signaling pathway or neutralizing TGF-β1 locally. Importantly, the micelle-hydrogel hybrid based localized therapy shows enhanced efficacy without local or systemic toxicity, which may represent a clinically relevant delivery platform in the management of renal interstitial fibrosis. Elsevier 2021-03 2020-10-18 /pmc/articles/PMC7982499/ /pubmed/33777685 http://dx.doi.org/10.1016/j.apsb.2020.10.016 Text en © 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Qin, Xianyan Xu, Yingying Zhou, Xu Gong, Tao Zhang, Zhi-Rong Fu, Yao An injectable micelle-hydrogel hybrid for localized and prolonged drug delivery in the management of renal fibrosis |
title | An injectable micelle-hydrogel hybrid for localized and prolonged drug delivery in the management of renal fibrosis |
title_full | An injectable micelle-hydrogel hybrid for localized and prolonged drug delivery in the management of renal fibrosis |
title_fullStr | An injectable micelle-hydrogel hybrid for localized and prolonged drug delivery in the management of renal fibrosis |
title_full_unstemmed | An injectable micelle-hydrogel hybrid for localized and prolonged drug delivery in the management of renal fibrosis |
title_short | An injectable micelle-hydrogel hybrid for localized and prolonged drug delivery in the management of renal fibrosis |
title_sort | injectable micelle-hydrogel hybrid for localized and prolonged drug delivery in the management of renal fibrosis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982499/ https://www.ncbi.nlm.nih.gov/pubmed/33777685 http://dx.doi.org/10.1016/j.apsb.2020.10.016 |
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