Effective Oxidation-Responsive Polyester Nanocarriers for Anti-Inflammatory Drug Delivery

Pan He,1 Bingtong Tang,1 Yusheng Li,1 Yu Zhang,2 Xinming Liu,2 Xin Guo,1 Dong Wang,3 Peng She,3,4 Chunsheng Xiao2 1School of Materials Science and Engineering, Changchun University of Science and Technology, Changchun, 130022, People’s Republic of China; 2Key Laboratory of Polymer Ecomaterials, Chan...

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Autores principales:	He P, Tang B, Li Y, Zhang Y, Liu X, Guo X, Wang D, She P, Xiao C
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	oxidation responsiveness pegylated polyesters nanosized micelles anti-inflammatory therapy curcumin delivery Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/06d5b688943541e1987a994843753b2e
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spelling	oai:doaj.org-article:06d5b688943541e1987a994843753b2e2021-12-02T15:06:16ZEffective Oxidation-Responsive Polyester Nanocarriers for Anti-Inflammatory Drug Delivery1178-2013https://doaj.org/article/06d5b688943541e1987a994843753b2e2021-07-01T00:00:00Zhttps://www.dovepress.com/effective-oxidation-responsive-polyester-nanocarriers-for-anti-inflamm-peer-reviewed-fulltext-article-IJNhttps://doaj.org/toc/1178-2013Pan He,1 Bingtong Tang,1 Yusheng Li,1 Yu Zhang,2 Xinming Liu,2 Xin Guo,1 Dong Wang,3 Peng She,3,4 Chunsheng Xiao2 1School of Materials Science and Engineering, Changchun University of Science and Technology, Changchun, 130022, People’s Republic of China; 2Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, People’s Republic of China; 3Department of Orthopaedics, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518107, People’s Republic of China; 4Joint Surgery Department, The First Hospital, Jilin University, Changchun, 130021, People’s Republic of ChinaCorrespondence: Pan He; Peng SheSchool of Materials Science and Engineering, Changchun University of Science and Technology, Changchun, 130022, People’s Republic of ChinaTel +86-431-85583188Fax +86-431-85583188Email hepan@cust.edu.cn; shep@mail.sysu.edu.cnBackground: High levels of oxidants, such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), are typical characteristics of an inflammatory microenvironment and are closely associated with a various inflammatory pathologies, eg, cancer, diabetes, atherosclerosis, and neurodegenerative diseases. Therefore, the delivery of anti-inflammatory drugs by oxidation-responsive smart systems would be an efficient anti-inflammatory strategy that benefits from the selective drug release in an inflammatory site, a lower treatment dose, and minimizes side effects.Purpose: In this study, we present the feasibility of an oxidation-sensitive PEGylated alternating polyester, methoxyl poly(ethylene glycol)-block-poly(phthalic anhydride-alter-glycidyl propargyl ether) (mPEG-b-P(PA-alt-GPBAe)), as novel nanocarrier for curcumin (CUR), and explore the application in anti-inflammatory therapy.Methods: The copolymers used were obtained by combining a click reaction and a ring-opening-polymerization method. CUR was loaded by self-assembly. The in vitro drug release, cytotoxicity toward RAW 264.7 cells and cellular uptake were investigated. Furthermore, the anti-inflammatory effects of CUR-loaded polymeric nanoparticles (NPs-CUR) were investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and tested in a murine model of ankle inflammation.Results: Fast drug release from NPs-CUR was observed in trigger of 1 mM H2O2 in PBS. Compared with NPs and free drugs, the significant anti-inflammatory potential of NPs-CUR was proven in activated RAW 264.7 cells by inhibiting the production of TNF-α, IL-1β, and IL-6 and increasing the level of an anti-inflammatory cytokine IL-10. Finally, a local injection of NPs-CUR at a dose of 0.25 mg/kg suppressed the acute ankle inflammatory response in mice by histological observation and further reduced the expression of pro-inflammatory cytokines in the affected ankle joints compared to that of free CUR.Conclusion: Both the significant in vitro and in vivo anti-inflammatory results indicated that our oxidation responsive polymeric nanoparticles are promising drug delivery systems for anti-inflammatory therapy.Keywords: oxidation responsiveness, PEGylated polyesters, nanosized micelles, anti-inflammatory therapy, curcumin deliveryHe PTang BLi YZhang YLiu XGuo XWang DShe PXiao CDove Medical Pressarticleoxidation responsivenesspegylated polyestersnanosized micellesanti-inflammatory therapycurcumin deliveryMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 5053-5064 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	oxidation responsiveness pegylated polyesters nanosized micelles anti-inflammatory therapy curcumin delivery Medicine (General) R5-920
spellingShingle	oxidation responsiveness pegylated polyesters nanosized micelles anti-inflammatory therapy curcumin delivery Medicine (General) R5-920 He P Tang B Li Y Zhang Y Liu X Guo X Wang D She P Xiao C Effective Oxidation-Responsive Polyester Nanocarriers for Anti-Inflammatory Drug Delivery
description	Pan He,1 Bingtong Tang,1 Yusheng Li,1 Yu Zhang,2 Xinming Liu,2 Xin Guo,1 Dong Wang,3 Peng She,3,4 Chunsheng Xiao2 1School of Materials Science and Engineering, Changchun University of Science and Technology, Changchun, 130022, People’s Republic of China; 2Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, People’s Republic of China; 3Department of Orthopaedics, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518107, People’s Republic of China; 4Joint Surgery Department, The First Hospital, Jilin University, Changchun, 130021, People’s Republic of ChinaCorrespondence: Pan He; Peng SheSchool of Materials Science and Engineering, Changchun University of Science and Technology, Changchun, 130022, People’s Republic of ChinaTel +86-431-85583188Fax +86-431-85583188Email hepan@cust.edu.cn; shep@mail.sysu.edu.cnBackground: High levels of oxidants, such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), are typical characteristics of an inflammatory microenvironment and are closely associated with a various inflammatory pathologies, eg, cancer, diabetes, atherosclerosis, and neurodegenerative diseases. Therefore, the delivery of anti-inflammatory drugs by oxidation-responsive smart systems would be an efficient anti-inflammatory strategy that benefits from the selective drug release in an inflammatory site, a lower treatment dose, and minimizes side effects.Purpose: In this study, we present the feasibility of an oxidation-sensitive PEGylated alternating polyester, methoxyl poly(ethylene glycol)-block-poly(phthalic anhydride-alter-glycidyl propargyl ether) (mPEG-b-P(PA-alt-GPBAe)), as novel nanocarrier for curcumin (CUR), and explore the application in anti-inflammatory therapy.Methods: The copolymers used were obtained by combining a click reaction and a ring-opening-polymerization method. CUR was loaded by self-assembly. The in vitro drug release, cytotoxicity toward RAW 264.7 cells and cellular uptake were investigated. Furthermore, the anti-inflammatory effects of CUR-loaded polymeric nanoparticles (NPs-CUR) were investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and tested in a murine model of ankle inflammation.Results: Fast drug release from NPs-CUR was observed in trigger of 1 mM H2O2 in PBS. Compared with NPs and free drugs, the significant anti-inflammatory potential of NPs-CUR was proven in activated RAW 264.7 cells by inhibiting the production of TNF-α, IL-1β, and IL-6 and increasing the level of an anti-inflammatory cytokine IL-10. Finally, a local injection of NPs-CUR at a dose of 0.25 mg/kg suppressed the acute ankle inflammatory response in mice by histological observation and further reduced the expression of pro-inflammatory cytokines in the affected ankle joints compared to that of free CUR.Conclusion: Both the significant in vitro and in vivo anti-inflammatory results indicated that our oxidation responsive polymeric nanoparticles are promising drug delivery systems for anti-inflammatory therapy.Keywords: oxidation responsiveness, PEGylated polyesters, nanosized micelles, anti-inflammatory therapy, curcumin delivery
format	article
author	He P Tang B Li Y Zhang Y Liu X Guo X Wang D She P Xiao C
author_facet	He P Tang B Li Y Zhang Y Liu X Guo X Wang D She P Xiao C
author_sort	He P
title	Effective Oxidation-Responsive Polyester Nanocarriers for Anti-Inflammatory Drug Delivery
title_short	Effective Oxidation-Responsive Polyester Nanocarriers for Anti-Inflammatory Drug Delivery
title_full	Effective Oxidation-Responsive Polyester Nanocarriers for Anti-Inflammatory Drug Delivery
title_fullStr	Effective Oxidation-Responsive Polyester Nanocarriers for Anti-Inflammatory Drug Delivery
title_full_unstemmed	Effective Oxidation-Responsive Polyester Nanocarriers for Anti-Inflammatory Drug Delivery
title_sort	effective oxidation-responsive polyester nanocarriers for anti-inflammatory drug delivery
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/06d5b688943541e1987a994843753b2e
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_version_	1718388492781748224

Effective Oxidation-Responsive Polyester Nanocarriers for Anti-Inflammatory Drug Delivery

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