Controlled release of Clenbuterol from a hydroxyapatite carrier for the treatment of Alzheimer’s Disease
Abstract Background Alzheimer’s disease is a neurodegenerative disorder, and Aβ aggregation is considered to be the central process implicated in its pathogenesis. Current treatments are faced by challenges such as serious side effects and reduced drug bioavailability. In this study, we developed a...
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| Format: | Article |
| Language: | English |
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American Association for the Advancement of Science (AAAS)
2023-10-01
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| Series: | Biomaterials Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40824-023-00432-4 |
| _version_ | 1827331168273432576 |
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| author | Yi-Wen Lin Chih-Hsiang Fang Ya-Jyun Liang Ching-Yun Yang Wei-Ting Kuo Feng-Huei Lin |
| author_facet | Yi-Wen Lin Chih-Hsiang Fang Ya-Jyun Liang Ching-Yun Yang Wei-Ting Kuo Feng-Huei Lin |
| author_sort | Yi-Wen Lin |
| collection | DOAJ |
| description | Abstract Background Alzheimer’s disease is a neurodegenerative disorder, and Aβ aggregation is considered to be the central process implicated in its pathogenesis. Current treatments are faced by challenges such as serious side effects and reduced drug bioavailability. In this study, we developed a drug delivery system for intramuscular injection that uses cellular activity to achieve constant and long-term drug release. Methods Synthesized mesoporous hydroxyapatite (SHAP) was prepared via co-precipitation, and hydrophobic surface modification using stearic acid was then used to load clenbuterol by physical absorption, thus creating the drug delivery system. Clenbuterol release was achieved through cellular activity, with macrophage uptake triggering lysosome/endosome disruption, cytoplasmic release, extracellular exocytosis, and subsequent systemic circulation. Results We found that clenbuterol-loaded SHAP enabled sustained release for more than 2 weeks and effectively modulated inflammation, reduced Aβ oligomer-induced toxicity, and prevented Aβ aggregation. Conclusions Our findings suggest that treatment with clenbuterol loaded in this SHAP delivery system could be a promising strategy for treating Alzheimer’s disease. Graphical Abstract |
| first_indexed | 2024-03-07T16:31:13Z |
| format | Article |
| id | doaj.art-116f929115e645dcb6cc1b91239d8ca0 |
| institution | Directory Open Access Journal |
| issn | 2055-7124 |
| language | English |
| last_indexed | 2024-03-07T16:31:13Z |
| publishDate | 2023-10-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | Article |
| series | Biomaterials Research |
| spelling | doaj.art-116f929115e645dcb6cc1b91239d8ca02024-03-03T10:11:27ZengAmerican Association for the Advancement of Science (AAAS)Biomaterials Research2055-71242023-10-0127111910.1186/s40824-023-00432-4Controlled release of Clenbuterol from a hydroxyapatite carrier for the treatment of Alzheimer’s DiseaseYi-Wen Lin0Chih-Hsiang Fang1Ya-Jyun Liang2Ching-Yun Yang3Wei-Ting Kuo4Feng-Huei Lin5Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan UniversityNational Taiwan University HospitalInstitute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan UniversityInstitute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan UniversityInstitute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan UniversityInstitute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan UniversityAbstract Background Alzheimer’s disease is a neurodegenerative disorder, and Aβ aggregation is considered to be the central process implicated in its pathogenesis. Current treatments are faced by challenges such as serious side effects and reduced drug bioavailability. In this study, we developed a drug delivery system for intramuscular injection that uses cellular activity to achieve constant and long-term drug release. Methods Synthesized mesoporous hydroxyapatite (SHAP) was prepared via co-precipitation, and hydrophobic surface modification using stearic acid was then used to load clenbuterol by physical absorption, thus creating the drug delivery system. Clenbuterol release was achieved through cellular activity, with macrophage uptake triggering lysosome/endosome disruption, cytoplasmic release, extracellular exocytosis, and subsequent systemic circulation. Results We found that clenbuterol-loaded SHAP enabled sustained release for more than 2 weeks and effectively modulated inflammation, reduced Aβ oligomer-induced toxicity, and prevented Aβ aggregation. Conclusions Our findings suggest that treatment with clenbuterol loaded in this SHAP delivery system could be a promising strategy for treating Alzheimer’s disease. Graphical Abstracthttps://doi.org/10.1186/s40824-023-00432-4Alzheimer’s diseaseAmyloid betaClenbuterolHydroxyapatiteControlled release |
| spellingShingle | Yi-Wen Lin Chih-Hsiang Fang Ya-Jyun Liang Ching-Yun Yang Wei-Ting Kuo Feng-Huei Lin Controlled release of Clenbuterol from a hydroxyapatite carrier for the treatment of Alzheimer’s Disease Biomaterials Research Alzheimer’s disease Amyloid beta Clenbuterol Hydroxyapatite Controlled release |
| title | Controlled release of Clenbuterol from a hydroxyapatite carrier for the treatment of Alzheimer’s Disease |
| title_full | Controlled release of Clenbuterol from a hydroxyapatite carrier for the treatment of Alzheimer’s Disease |
| title_fullStr | Controlled release of Clenbuterol from a hydroxyapatite carrier for the treatment of Alzheimer’s Disease |
| title_full_unstemmed | Controlled release of Clenbuterol from a hydroxyapatite carrier for the treatment of Alzheimer’s Disease |
| title_short | Controlled release of Clenbuterol from a hydroxyapatite carrier for the treatment of Alzheimer’s Disease |
| title_sort | controlled release of clenbuterol from a hydroxyapatite carrier for the treatment of alzheimer s disease |
| topic | Alzheimer’s disease Amyloid beta Clenbuterol Hydroxyapatite Controlled release |
| url | https://doi.org/10.1186/s40824-023-00432-4 |
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