國家衛生研究院 NHRI:Item 3990099045/15882

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Title:	Macrophage-mediated controlled release of cysteine protease inhibitor from PLGA-PEG/hydroxyapatite microspheres for targeting cathepsin S in Alzheimer's disease
Authors:	Yang, IH;Kuan, CY;Zhang, SL;Chen, ZY;Li, CH;Liang, YJ;Kuo, WT;Chang, CT;Lin, J;Hsieh, HP;Chang, JY;Lin, FH
Contributors:	Institute of Biomedical Engineering and Nanomedicine;Institute of Biotechnology and Pharmaceutical Research
Abstract:	The cause of Alzheimer's disease (AD) remains unknown; however, studies have indicated the increased expression of cathepsin S (CTSS) in AD brains. Cathepsin S acts as a β-secretase, prompting the release of amyloid-β peptides and stimulating microglial cell activation, causing microglial migration, and contributing to neuroinflammation and disease progression. In this study, CT001, an inhibitor of the cysteine protease CTSS, was encapsulated in poly(lactic-co-glycolic acid)-polyethylene glycol microspheres combined with hydroxyapatite microspheres (CPPMs/HAMs) to achieve a constant and long-term drug release for AD. The results showed that CPPMs/HAMs had a uniform diameter of approximately 1 μm, enabling macrophage endocytosis and facilitating sustained CT001 release into the bloodstream, ultimately reaching the brain for AD treatment. The developed CPPMs/HAMs demonstrated excellent anti-inflammatory properties and mitigated CTSS expression in an in vitro inflammation microglial model. Intramuscular administration of CPPMs/HAMs improved learning and memory in AD mice during behavioral assessments. Furthermore, CPPMs/HAMs reduced CTSS expression, amyloid-beta accumulation, and deposition in vivo. This study demonstrated the potential of CT001 delivered via CPPMs/HAMs as a promising approach for managing AD in patients.
Date:	2024-06-24
Relation:	European Polymer Journal. 2024 Jun 24;214:Article number 113151.
Link to:	http://dx.doi.org/10.1016/j.eurpolymj.2024.113151
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0014-3057&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:001248191300001
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85194457249
Appears in Collections:	[Feng-Huei Lin] Periodical Articles [Hsing-Pang Hsieh] Periodical Articles [Jang-Yang Chang] Periodical Articles

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