Injectable Hierarchical Bioactive Hydrogels with Fibroblast Growth Factor 21/Edaravone/Caffeic Acid Asynchronous Delivery for Treating Parkinson's Disease
Abstract Parkinson's disease (PD) is one of the most common long‐term neurodegenerative disorders, with multiple comorbid psychiatric and behavioral abnormalities. The combination of clinical drugs targeting different symptoms with smart hydrogels to achieve asynchronous releases is highly tran...
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202412020 |
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| author | Junpeng Xu Peng Dai Chen Zhang Na Dong Caiyan Li Chonghui Tang Zhihao Jin Shih‐Ho Lin Luyang Ye Tianmiao Sun Yukai Jin Fenzan Wu Lihua Luo Ping Wu Shengcun Li Xiaokun Li Shan‐hui Hsu Dawei Jiang Zhouguang Wang |
| author_facet | Junpeng Xu Peng Dai Chen Zhang Na Dong Caiyan Li Chonghui Tang Zhihao Jin Shih‐Ho Lin Luyang Ye Tianmiao Sun Yukai Jin Fenzan Wu Lihua Luo Ping Wu Shengcun Li Xiaokun Li Shan‐hui Hsu Dawei Jiang Zhouguang Wang |
| author_sort | Junpeng Xu |
| collection | DOAJ |
| description | Abstract Parkinson's disease (PD) is one of the most common long‐term neurodegenerative disorders, with multiple comorbid psychiatric and behavioral abnormalities. The combination of clinical drugs targeting different symptoms with smart hydrogels to achieve asynchronous releases is highly translational and challenging. Here, a hierarchical bioactive hydrogel (OACDP) is designed with asynchronous release based on PD pathology. The hydrogel with caffeic acid‐grafted polymer main chain is crosslinked using a micellar nanocrosslinker, with sufficient modulus (≈167 Pa), antioxidant activity (> 50%), injectability (30‐gauge syringe needle), and shape‐adaptability. Each of the three drugs (caffeic acid, fibroblast growth factor 21, and Edaravone) is separately engaged in different micro‐ or nanostructures of the hydrogel and released with asynchronous kinetics of first‐order release, zero‐order release, or matching Korsmeyer–Peppas model. The triple‐loaded hydrogel is injected into the brains of PD rats, showing behavioral improvement. Histological analysis revealed that the triple‐loaded OACDP hydrogels are effective in achieving immediate neuroprotection, i.e., reduction the loss of tyrosine hydroxylase in substantia nigra compacta and striatum (retained ≈10‐fold versus control), decreasing oxidative stress, reducing astrocyte and microglia activation, and stimulating the AMPK/PGC‐1α axis to regulate the mitochondrial function, providing a multi‐dimensional PD therapy. The asynchronous release of OACDP hydrogel provides a new conception for PD treatment and other neurodegenerative diseases. |
| format | Article |
| id | doaj-art-d40a263960cb495192fedb6e9b2971ec |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-d40a263960cb495192fedb6e9b2971ec2025-01-29T09:50:19ZengWileyAdvanced Science2198-38442025-01-01124n/an/a10.1002/advs.202412020Injectable Hierarchical Bioactive Hydrogels with Fibroblast Growth Factor 21/Edaravone/Caffeic Acid Asynchronous Delivery for Treating Parkinson's DiseaseJunpeng Xu0Peng Dai1Chen Zhang2Na Dong3Caiyan Li4Chonghui Tang5Zhihao Jin6Shih‐Ho Lin7Luyang Ye8Tianmiao Sun9Yukai Jin10Fenzan Wu11Lihua Luo12Ping Wu13Shengcun Li14Xiaokun Li15Shan‐hui Hsu16Dawei Jiang17Zhouguang Wang18Affiliated Cixi Hospital Wenzhou Medical University Ningbo Zhejiang 315300 ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health) School of Pharmaceutical Science Wenzhou Medical University Wenzhou Zhejiang 325000 ChinaSchool and Hospital of Stomatology Wenzhou Medical University Wenzhou Zhejiang 324025 ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health) School of Pharmaceutical Science Wenzhou Medical University Wenzhou Zhejiang 325000 ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health) School of Pharmaceutical Science Wenzhou Medical University Wenzhou Zhejiang 325000 ChinaAffiliated Cixi Hospital Wenzhou Medical University Ningbo Zhejiang 315300 ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health) School of Pharmaceutical Science Wenzhou Medical University Wenzhou Zhejiang 325000 ChinaInstitute of Polymer Science and Engineering National Taiwan University Taipei Taiwan 106319 Republic of ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health) School of Pharmaceutical Science Wenzhou Medical University Wenzhou Zhejiang 325000 ChinaAffiliated Cixi Hospital Wenzhou Medical University Ningbo Zhejiang 315300 ChinaAffiliated Cixi Hospital Wenzhou Medical University Ningbo Zhejiang 315300 ChinaAffiliated Cixi Hospital Wenzhou Medical University Ningbo Zhejiang 315300 ChinaSchool and Hospital of Stomatology Wenzhou Medical University Wenzhou Zhejiang 324025 ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health) School of Pharmaceutical Science Wenzhou Medical University Wenzhou Zhejiang 325000 ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health) School of Pharmaceutical Science Wenzhou Medical University Wenzhou Zhejiang 325000 ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health) School of Pharmaceutical Science Wenzhou Medical University Wenzhou Zhejiang 325000 ChinaInstitute of Polymer Science and Engineering National Taiwan University Taipei Taiwan 106319 Republic of ChinaAffiliated Cixi Hospital Wenzhou Medical University Ningbo Zhejiang 315300 ChinaOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health) School of Pharmaceutical Science Wenzhou Medical University Wenzhou Zhejiang 325000 ChinaAbstract Parkinson's disease (PD) is one of the most common long‐term neurodegenerative disorders, with multiple comorbid psychiatric and behavioral abnormalities. The combination of clinical drugs targeting different symptoms with smart hydrogels to achieve asynchronous releases is highly translational and challenging. Here, a hierarchical bioactive hydrogel (OACDP) is designed with asynchronous release based on PD pathology. The hydrogel with caffeic acid‐grafted polymer main chain is crosslinked using a micellar nanocrosslinker, with sufficient modulus (≈167 Pa), antioxidant activity (> 50%), injectability (30‐gauge syringe needle), and shape‐adaptability. Each of the three drugs (caffeic acid, fibroblast growth factor 21, and Edaravone) is separately engaged in different micro‐ or nanostructures of the hydrogel and released with asynchronous kinetics of first‐order release, zero‐order release, or matching Korsmeyer–Peppas model. The triple‐loaded hydrogel is injected into the brains of PD rats, showing behavioral improvement. Histological analysis revealed that the triple‐loaded OACDP hydrogels are effective in achieving immediate neuroprotection, i.e., reduction the loss of tyrosine hydroxylase in substantia nigra compacta and striatum (retained ≈10‐fold versus control), decreasing oxidative stress, reducing astrocyte and microglia activation, and stimulating the AMPK/PGC‐1α axis to regulate the mitochondrial function, providing a multi‐dimensional PD therapy. The asynchronous release of OACDP hydrogel provides a new conception for PD treatment and other neurodegenerative diseases.https://doi.org/10.1002/advs.202412020asynchronous releasebioactive hydrogelfibroblast growth factorParkinson's diseasetriple‐drug delivery system |
| spellingShingle | Junpeng Xu Peng Dai Chen Zhang Na Dong Caiyan Li Chonghui Tang Zhihao Jin Shih‐Ho Lin Luyang Ye Tianmiao Sun Yukai Jin Fenzan Wu Lihua Luo Ping Wu Shengcun Li Xiaokun Li Shan‐hui Hsu Dawei Jiang Zhouguang Wang Injectable Hierarchical Bioactive Hydrogels with Fibroblast Growth Factor 21/Edaravone/Caffeic Acid Asynchronous Delivery for Treating Parkinson's Disease Advanced Science asynchronous release bioactive hydrogel fibroblast growth factor Parkinson's disease triple‐drug delivery system |
| title | Injectable Hierarchical Bioactive Hydrogels with Fibroblast Growth Factor 21/Edaravone/Caffeic Acid Asynchronous Delivery for Treating Parkinson's Disease |
| title_full | Injectable Hierarchical Bioactive Hydrogels with Fibroblast Growth Factor 21/Edaravone/Caffeic Acid Asynchronous Delivery for Treating Parkinson's Disease |
| title_fullStr | Injectable Hierarchical Bioactive Hydrogels with Fibroblast Growth Factor 21/Edaravone/Caffeic Acid Asynchronous Delivery for Treating Parkinson's Disease |
| title_full_unstemmed | Injectable Hierarchical Bioactive Hydrogels with Fibroblast Growth Factor 21/Edaravone/Caffeic Acid Asynchronous Delivery for Treating Parkinson's Disease |
| title_short | Injectable Hierarchical Bioactive Hydrogels with Fibroblast Growth Factor 21/Edaravone/Caffeic Acid Asynchronous Delivery for Treating Parkinson's Disease |
| title_sort | injectable hierarchical bioactive hydrogels with fibroblast growth factor 21 edaravone caffeic acid asynchronous delivery for treating parkinson s disease |
| topic | asynchronous release bioactive hydrogel fibroblast growth factor Parkinson's disease triple‐drug delivery system |
| url | https://doi.org/10.1002/advs.202412020 |
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