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”...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-03-01
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| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383520307681 |
| _version_ | 1818848308475461632 |
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| author | Xianyan Qin Yingying Xu Xu Zhou Tao Gong Zhi-Rong Zhang Yao Fu |
| author_facet | Xianyan Qin Yingying Xu Xu Zhou Tao Gong Zhi-Rong Zhang Yao Fu |
| author_sort | Xianyan Qin |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T06:15:17Z |
| format | Article |
| id | doaj.art-d6d64f67c19141cca0381fb0bc596ed5 |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-12-19T06:15:17Z |
| publishDate | 2021-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-d6d64f67c19141cca0381fb0bc596ed52022-12-21T20:32:52ZengElsevierActa Pharmaceutica Sinica B2211-38352021-03-01113835847An injectable micelle-hydrogel hybrid for localized and prolonged drug delivery in the management of renal fibrosisXianyan Qin0Yingying Xu1Xu Zhou2Tao Gong3Zhi-Rong Zhang4Yao Fu5Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China; Key Laboratory of Advanced Technologies of Materials, Ministry of Education and School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China; Sichuan Provincial Orthopedic Hospital, Chengdu 610041, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2211383520307681Hydrogel“Plum‒pudding” structureLocalized therapyControlled releaseRenal fibrosisInflammation |
| spellingShingle | Xianyan Qin Yingying Xu Xu Zhou Tao Gong Zhi-Rong Zhang Yao Fu An injectable micelle-hydrogel hybrid for localized and prolonged drug delivery in the management of renal fibrosis Acta Pharmaceutica Sinica B Hydrogel “Plum‒pudding” structure Localized therapy Controlled release Renal fibrosis Inflammation |
| 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 | Hydrogel “Plum‒pudding” structure Localized therapy Controlled release Renal fibrosis Inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S2211383520307681 |
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