In Situ Forming Injectable Hydrogel For Encapsulation Of Nanoiguratimod And Sustained Release Of Therapeutics

Zhenzhen Ma,1,* Cheng Tao,2,* Lin Sun,1 Shengbei Qi,2 Yuan Le,2,3 Jiexin Wang,2–4 Changhong Li,1 Xiangyuan Liu,1 Jianjun Zhang,2 Jinxia Zhao1 1Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing 100191, People’s Republic of China; 2College of Chem...

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Autores principales:	Ma Z, Tao C, Sun L, Qi S, Le Y, Wang J, Li C, Liu X, Zhang J, Zhao J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	iguratimod nanoparticles injectable hydrogel rheumatoid arthritis drug sustained release system Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/d4e4845dc3f44eca8646c9122405ae8c
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spelling	oai:doaj.org-article:d4e4845dc3f44eca8646c9122405ae8c2021-12-02T08:29:36ZIn Situ Forming Injectable Hydrogel For Encapsulation Of Nanoiguratimod And Sustained Release Of Therapeutics1178-2013https://doaj.org/article/d4e4845dc3f44eca8646c9122405ae8c2019-11-01T00:00:00Zhttps://www.dovepress.com/in-situ-forming-injectable-hydrogel-for-encapsulation-of-nanoiguratimo-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Zhenzhen Ma,1,* Cheng Tao,2,* Lin Sun,1 Shengbei Qi,2 Yuan Le,2,3 Jiexin Wang,2–4 Changhong Li,1 Xiangyuan Liu,1 Jianjun Zhang,2 Jinxia Zhao1 1Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing 100191, People’s Republic of China; 2College of Chemical Engineering, Beijing University of Chemical Technology, Beijing 100029, People’s Republic of China; 3Research Center of the Ministry of Education for High Gravity Engineering and Technology, Beijing University of Chemical Technology, Beijing 100029, People’s Republic of China; 4Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianjun Zhang; Jinxia Zhao Email zhangjj@mail.buct.edu.cn; zhao-jinxia@163.comBackground: Iguratimod (IGUR) is a novel disease-modifying antirheumatic drug used for treating rheumatoid arthritis (RA). To improve its bioavailability and to alleviate gastrointestinal side effects, we changed the formulation into nanoiguratimod-loaded hydrogel (NanoIGUR-loaded hydrogel) composites for sustained release of therapeutics.Methods: IGUR was first encapsulated in biodegradable polyvinyl alcohol micelle by liquid antisolvent precipitation (LAP) technology, and then loaded into an in situ injectable hyaluronic acid hydrogel, which was cross-linked by PEG (Thiol)2 (HS-PEG-SH) through Michael addition reaction. In vitro, the biological effects (proliferation, migration, and invasion) of NanoIGUR-loaded hydrogel on fibroblast-like synoviocytes (RA-FLS) from RA patients were evaluated. In vivo, the pharmacokinetics of NanoIGUR-loaded hydrogel was assessed and the efficacy of NanoIGUR-loaded hydrogel in treating collagen-induced arthritis (CIA) rats was evaluated.Results: By the LAP technique, we acquired the amorphous form nanoiguratimod, with an average size of 458 nm, which had higher dissolution rates and higher stability. The release of IGUR from hydrogel composite in PBS was gradual and sustained for up to 72 hrs compared with nanoiguratimod. Different concentrations of NanoIGUR-loaded hydrogel inhibited the proliferation, migration, and invasion of RA-FLS. The pharmacokinetic parameters showed better bioavailability and longer half-life time with NanoIGUR-loaded hydrogel by subcutaneous administration than oral raw iguratimod. Animal experiments confirmed that subcutaneous injection of NanoIGUR-loaded hydrogel (10 mg/kg every 3 days) and oral raw iguratimod (10mg/kg daily) showed similar efficacy in decreasing arthritis index score, pathological score, and expression of inflammatory cytokines.Conclusion: Overall, we demonstrate that NanoIGUR-loaded hydrogel provides a new route of administration and extends the administration interval. It could be a promising drug-delivery approach in the management of RA.Keywords: iguratimod, nanoparticles, injectable hydrogel, rheumatoid arthritis, drug sustained-release systemMa ZTao CSun LQi SLe YWang JLi CLiu XZhang JZhao JDove Medical Pressarticleiguratimodnanoparticlesinjectable hydrogelrheumatoid arthritisdrug sustained release systemMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 8725-8738 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	iguratimod nanoparticles injectable hydrogel rheumatoid arthritis drug sustained release system Medicine (General) R5-920
spellingShingle	iguratimod nanoparticles injectable hydrogel rheumatoid arthritis drug sustained release system Medicine (General) R5-920 Ma Z Tao C Sun L Qi S Le Y Wang J Li C Liu X Zhang J Zhao J In Situ Forming Injectable Hydrogel For Encapsulation Of Nanoiguratimod And Sustained Release Of Therapeutics
description	Zhenzhen Ma,1,* Cheng Tao,2,* Lin Sun,1 Shengbei Qi,2 Yuan Le,2,3 Jiexin Wang,2–4 Changhong Li,1 Xiangyuan Liu,1 Jianjun Zhang,2 Jinxia Zhao1 1Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing 100191, People’s Republic of China; 2College of Chemical Engineering, Beijing University of Chemical Technology, Beijing 100029, People’s Republic of China; 3Research Center of the Ministry of Education for High Gravity Engineering and Technology, Beijing University of Chemical Technology, Beijing 100029, People’s Republic of China; 4Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianjun Zhang; Jinxia Zhao Email zhangjj@mail.buct.edu.cn; zhao-jinxia@163.comBackground: Iguratimod (IGUR) is a novel disease-modifying antirheumatic drug used for treating rheumatoid arthritis (RA). To improve its bioavailability and to alleviate gastrointestinal side effects, we changed the formulation into nanoiguratimod-loaded hydrogel (NanoIGUR-loaded hydrogel) composites for sustained release of therapeutics.Methods: IGUR was first encapsulated in biodegradable polyvinyl alcohol micelle by liquid antisolvent precipitation (LAP) technology, and then loaded into an in situ injectable hyaluronic acid hydrogel, which was cross-linked by PEG (Thiol)2 (HS-PEG-SH) through Michael addition reaction. In vitro, the biological effects (proliferation, migration, and invasion) of NanoIGUR-loaded hydrogel on fibroblast-like synoviocytes (RA-FLS) from RA patients were evaluated. In vivo, the pharmacokinetics of NanoIGUR-loaded hydrogel was assessed and the efficacy of NanoIGUR-loaded hydrogel in treating collagen-induced arthritis (CIA) rats was evaluated.Results: By the LAP technique, we acquired the amorphous form nanoiguratimod, with an average size of 458 nm, which had higher dissolution rates and higher stability. The release of IGUR from hydrogel composite in PBS was gradual and sustained for up to 72 hrs compared with nanoiguratimod. Different concentrations of NanoIGUR-loaded hydrogel inhibited the proliferation, migration, and invasion of RA-FLS. The pharmacokinetic parameters showed better bioavailability and longer half-life time with NanoIGUR-loaded hydrogel by subcutaneous administration than oral raw iguratimod. Animal experiments confirmed that subcutaneous injection of NanoIGUR-loaded hydrogel (10 mg/kg every 3 days) and oral raw iguratimod (10mg/kg daily) showed similar efficacy in decreasing arthritis index score, pathological score, and expression of inflammatory cytokines.Conclusion: Overall, we demonstrate that NanoIGUR-loaded hydrogel provides a new route of administration and extends the administration interval. It could be a promising drug-delivery approach in the management of RA.Keywords: iguratimod, nanoparticles, injectable hydrogel, rheumatoid arthritis, drug sustained-release system
format	article
author	Ma Z Tao C Sun L Qi S Le Y Wang J Li C Liu X Zhang J Zhao J
author_facet	Ma Z Tao C Sun L Qi S Le Y Wang J Li C Liu X Zhang J Zhao J
author_sort	Ma Z
title	In Situ Forming Injectable Hydrogel For Encapsulation Of Nanoiguratimod And Sustained Release Of Therapeutics
title_short	In Situ Forming Injectable Hydrogel For Encapsulation Of Nanoiguratimod And Sustained Release Of Therapeutics
title_full	In Situ Forming Injectable Hydrogel For Encapsulation Of Nanoiguratimod And Sustained Release Of Therapeutics
title_fullStr	In Situ Forming Injectable Hydrogel For Encapsulation Of Nanoiguratimod And Sustained Release Of Therapeutics
title_full_unstemmed	In Situ Forming Injectable Hydrogel For Encapsulation Of Nanoiguratimod And Sustained Release Of Therapeutics
title_sort	in situ forming injectable hydrogel for encapsulation of nanoiguratimod and sustained release of therapeutics
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/d4e4845dc3f44eca8646c9122405ae8c
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In Situ Forming Injectable Hydrogel For Encapsulation Of Nanoiguratimod And Sustained Release Of Therapeutics

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