Targeted acetylcholinesterase-responsive drug carriers with long duration of drug action and reduced hepatotoxicity

Yulong Lin, Yalin Wang, Jie Lv, Nannan Wang, Jing Wang, Meng LiCollege of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang 050017, People’s Republic of ChinaPurpose: Acetylcholinesterase (AChE) plays a critical role in the transmission of nerve impulse at the cholinergic syn...

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Autores principales:	Lin Y, Wang Y, Lv J, Wang N, Wang J, Li M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	Acetylcholinesterase inhibitor controlled drug release mesoporous silica nanoparticles drug action hepatotoxicity Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/0d686f4cae024fb98b70cdede6a6f4d0
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spelling	oai:doaj.org-article:0d686f4cae024fb98b70cdede6a6f4d02021-12-02T00:01:46ZTargeted acetylcholinesterase-responsive drug carriers with long duration of drug action and reduced hepatotoxicity1178-2013https://doaj.org/article/0d686f4cae024fb98b70cdede6a6f4d02019-07-01T00:00:00Zhttps://www.dovepress.com/targeted-acetylcholinesterase-responsive-drug-carriers-with-long-durat-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yulong Lin, Yalin Wang, Jie Lv, Nannan Wang, Jing Wang, Meng LiCollege of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang 050017, People’s Republic of ChinaPurpose: Acetylcholinesterase (AChE) plays a critical role in the transmission of nerve impulse at the cholinergic synapses. Design and synthesis of AChE inhibitors that increase the cholinergic transmission by blocking the degradation of acetylcholine can serve as a strategy for the treatment of AChE-associated disease. Herein, an operational targeted drug delivery platform based on AChE-responsive system has been presented by combining the unique properties of enzyme-controlled mesoporous silica nanoparticles (MSN) with clinical-used AChE inhibitor.Methods: Functionalized MSNs were synthesized by liquid phase method and characterized by using different analytical methods. The biocompatibility and cytotoxicity of MSNs were determined by hemolysis experiment and MTT assay, respectively. Comparison of AChE activity between drug-loading system and inhibitor was developed with kits and by ELISA method. The efficacy of drug-loaded nanocarriers was investigated in a mouse model.Results: Compared with AChE inhibitor itself, the inhibition efficiency of this drug delivery system was strongly dependent on the concentration of AChE. Only AChE with high concentration could cause the opening of pores in the MSN, leading to the controlled release of AChE inhibitor in disease condition. Critically, the drug delivery system can not only exhibit long duration of drug action on AChE inhibition but also reduce the hepatotoxicity in vivo.Conclusion: In summary, AChE-responsive drug release systems have been far less explored. Our results would shed lights on the design of enzyme controlled-release multifunctional system for enzyme-associated disease treatment.Keywords: acetylcholinesterase inhibitor, controlled drug release, mesoporous silica nanoparticles, drug action, hepatotoxicityLin YWang YLv JWang NWang JLi MDove Medical PressarticleAcetylcholinesterase inhibitorcontrolled drug releasemesoporous silica nanoparticlesdrug actionhepatotoxicityMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 5817-5829 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Acetylcholinesterase inhibitor controlled drug release mesoporous silica nanoparticles drug action hepatotoxicity Medicine (General) R5-920
spellingShingle	Acetylcholinesterase inhibitor controlled drug release mesoporous silica nanoparticles drug action hepatotoxicity Medicine (General) R5-920 Lin Y Wang Y Lv J Wang N Wang J Li M Targeted acetylcholinesterase-responsive drug carriers with long duration of drug action and reduced hepatotoxicity
description	Yulong Lin, Yalin Wang, Jie Lv, Nannan Wang, Jing Wang, Meng LiCollege of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang 050017, People’s Republic of ChinaPurpose: Acetylcholinesterase (AChE) plays a critical role in the transmission of nerve impulse at the cholinergic synapses. Design and synthesis of AChE inhibitors that increase the cholinergic transmission by blocking the degradation of acetylcholine can serve as a strategy for the treatment of AChE-associated disease. Herein, an operational targeted drug delivery platform based on AChE-responsive system has been presented by combining the unique properties of enzyme-controlled mesoporous silica nanoparticles (MSN) with clinical-used AChE inhibitor.Methods: Functionalized MSNs were synthesized by liquid phase method and characterized by using different analytical methods. The biocompatibility and cytotoxicity of MSNs were determined by hemolysis experiment and MTT assay, respectively. Comparison of AChE activity between drug-loading system and inhibitor was developed with kits and by ELISA method. The efficacy of drug-loaded nanocarriers was investigated in a mouse model.Results: Compared with AChE inhibitor itself, the inhibition efficiency of this drug delivery system was strongly dependent on the concentration of AChE. Only AChE with high concentration could cause the opening of pores in the MSN, leading to the controlled release of AChE inhibitor in disease condition. Critically, the drug delivery system can not only exhibit long duration of drug action on AChE inhibition but also reduce the hepatotoxicity in vivo.Conclusion: In summary, AChE-responsive drug release systems have been far less explored. Our results would shed lights on the design of enzyme controlled-release multifunctional system for enzyme-associated disease treatment.Keywords: acetylcholinesterase inhibitor, controlled drug release, mesoporous silica nanoparticles, drug action, hepatotoxicity
format	article
author	Lin Y Wang Y Lv J Wang N Wang J Li M
author_facet	Lin Y Wang Y Lv J Wang N Wang J Li M
author_sort	Lin Y
title	Targeted acetylcholinesterase-responsive drug carriers with long duration of drug action and reduced hepatotoxicity
title_short	Targeted acetylcholinesterase-responsive drug carriers with long duration of drug action and reduced hepatotoxicity
title_full	Targeted acetylcholinesterase-responsive drug carriers with long duration of drug action and reduced hepatotoxicity
title_fullStr	Targeted acetylcholinesterase-responsive drug carriers with long duration of drug action and reduced hepatotoxicity
title_full_unstemmed	Targeted acetylcholinesterase-responsive drug carriers with long duration of drug action and reduced hepatotoxicity
title_sort	targeted acetylcholinesterase-responsive drug carriers with long duration of drug action and reduced hepatotoxicity
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/0d686f4cae024fb98b70cdede6a6f4d0
work_keys_str_mv	AT liny targetedacetylcholinesteraseresponsivedrugcarrierswithlongdurationofdrugactionandreducedhepatotoxicity AT wangy targetedacetylcholinesteraseresponsivedrugcarrierswithlongdurationofdrugactionandreducedhepatotoxicity AT lvj targetedacetylcholinesteraseresponsivedrugcarrierswithlongdurationofdrugactionandreducedhepatotoxicity AT wangn targetedacetylcholinesteraseresponsivedrugcarrierswithlongdurationofdrugactionandreducedhepatotoxicity AT wangj targetedacetylcholinesteraseresponsivedrugcarrierswithlongdurationofdrugactionandreducedhepatotoxicity AT lim targetedacetylcholinesteraseresponsivedrugcarrierswithlongdurationofdrugactionandreducedhepatotoxicity
_version_	1718403966783455232

Targeted acetylcholinesterase-responsive drug carriers with long duration of drug action and reduced hepatotoxicity

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