Multifunctional folate receptor-targeting and pH-responsive nanocarriers loaded with methotrexate for treatment of rheumatoid arthritis

Jinlong Zhao,1 Menghui Zhao,1 Changhui Yu,1 Xueyan Zhang,1 Jiaxin Liu,1 Xinwei Cheng,2 Robert J Lee,1,2 Fengying Sun,1 Lesheng Teng,1 Youxin Li1 1School of Life Sciences, Jilin University, Changchun, China; 2College of Pharmacy, Ohio State University, Columbus, OH, USA Abstract: Rheumatoid arthrit...

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Autores principales:	Zhao J, Zhao M, Yu C, Zhang X, Liu J, Cheng X, Lee RJ, Sun F, Teng L, Li Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Rheumatoid arthritis Methotrexate nanoparticles Folate pH-responsive PCADK Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/e8fed8cfbfba4a26ae08766c2383c425
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spelling	oai:doaj.org-article:e8fed8cfbfba4a26ae08766c2383c4252021-12-02T00:31:21ZMultifunctional folate receptor-targeting and pH-responsive nanocarriers loaded with methotrexate for treatment of rheumatoid arthritis1178-2013https://doaj.org/article/e8fed8cfbfba4a26ae08766c2383c4252017-09-01T00:00:00Zhttps://www.dovepress.com/multifunctional-folate-receptor-targeting-and-ph-responsive-nanocarrie-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jinlong Zhao,1 Menghui Zhao,1 Changhui Yu,1 Xueyan Zhang,1 Jiaxin Liu,1 Xinwei Cheng,2 Robert J Lee,1,2 Fengying Sun,1 Lesheng Teng,1 Youxin Li1 1School of Life Sciences, Jilin University, Changchun, China; 2College of Pharmacy, Ohio State University, Columbus, OH, USA Abstract: Rheumatoid arthritis (RA) is an autoimmune disease characterized by progressive cartilage and bone destruction. Activated macrophages that overexpress folic acid (FA) receptors play an important role in RA, due to their abundance in inflamed synovial membrane and joints. In an effort to deliver drugs to the inflamed tissues, multifunctional FA receptor-targeting and pH-responsive nanocarriers were developed. They were composed of lipids, polyethylene glycol (PEG)–poly(lactic-co-glycolic acid) (PLGA) forming a hydrophilic shell, FA around the hydrophilic shell as a targeting ligand, and poly(cyclohexane-1,4-diylacetone dimethylene ketal) (PCADK) and PLGA as a hydrophobic core. PCADK also acts as a pH-responsive material. Methotrexate (Mtx) was encapsulated in the nanoparticles, which exhibited pH-responsive release in vitro. Cellular uptake and cytotoxicity experiments revealed that FA-PEG-PLGA/PCADK–lipid nanoparticles loaded with Mtx (FA-PPLNPs) exhibited superior cellular uptake and higher cytotoxicity to activated macrophages than PPLNPs/Mtx. The therapeutic effect of FA-PPLNPs/Mtx in RA was confirmed in an adjuvant-induced arthritis rat model. These results suggest that the multifunctional folate receptor-targeting and pH-responsive nanocarriers are promising for the treatment of RA. Keywords: rheumatoid arthritis, methotrexate, nanoparticles, folate, pH-responsive, PCADK Zhao JZhao MYu CZhang XLiu JCheng XLee RJSun FTeng LLi YDove Medical PressarticleRheumatoid arthritisMethotrexatenanoparticlesFolatepH-responsivePCADKMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 6735-6746 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Rheumatoid arthritis Methotrexate nanoparticles Folate pH-responsive PCADK Medicine (General) R5-920
spellingShingle	Rheumatoid arthritis Methotrexate nanoparticles Folate pH-responsive PCADK Medicine (General) R5-920 Zhao J Zhao M Yu C Zhang X Liu J Cheng X Lee RJ Sun F Teng L Li Y Multifunctional folate receptor-targeting and pH-responsive nanocarriers loaded with methotrexate for treatment of rheumatoid arthritis
description	Jinlong Zhao,1 Menghui Zhao,1 Changhui Yu,1 Xueyan Zhang,1 Jiaxin Liu,1 Xinwei Cheng,2 Robert J Lee,1,2 Fengying Sun,1 Lesheng Teng,1 Youxin Li1 1School of Life Sciences, Jilin University, Changchun, China; 2College of Pharmacy, Ohio State University, Columbus, OH, USA Abstract: Rheumatoid arthritis (RA) is an autoimmune disease characterized by progressive cartilage and bone destruction. Activated macrophages that overexpress folic acid (FA) receptors play an important role in RA, due to their abundance in inflamed synovial membrane and joints. In an effort to deliver drugs to the inflamed tissues, multifunctional FA receptor-targeting and pH-responsive nanocarriers were developed. They were composed of lipids, polyethylene glycol (PEG)–poly(lactic-co-glycolic acid) (PLGA) forming a hydrophilic shell, FA around the hydrophilic shell as a targeting ligand, and poly(cyclohexane-1,4-diylacetone dimethylene ketal) (PCADK) and PLGA as a hydrophobic core. PCADK also acts as a pH-responsive material. Methotrexate (Mtx) was encapsulated in the nanoparticles, which exhibited pH-responsive release in vitro. Cellular uptake and cytotoxicity experiments revealed that FA-PEG-PLGA/PCADK–lipid nanoparticles loaded with Mtx (FA-PPLNPs) exhibited superior cellular uptake and higher cytotoxicity to activated macrophages than PPLNPs/Mtx. The therapeutic effect of FA-PPLNPs/Mtx in RA was confirmed in an adjuvant-induced arthritis rat model. These results suggest that the multifunctional folate receptor-targeting and pH-responsive nanocarriers are promising for the treatment of RA. Keywords: rheumatoid arthritis, methotrexate, nanoparticles, folate, pH-responsive, PCADK
format	article
author	Zhao J Zhao M Yu C Zhang X Liu J Cheng X Lee RJ Sun F Teng L Li Y
author_facet	Zhao J Zhao M Yu C Zhang X Liu J Cheng X Lee RJ Sun F Teng L Li Y
author_sort	Zhao J
title	Multifunctional folate receptor-targeting and pH-responsive nanocarriers loaded with methotrexate for treatment of rheumatoid arthritis
title_short	Multifunctional folate receptor-targeting and pH-responsive nanocarriers loaded with methotrexate for treatment of rheumatoid arthritis
title_full	Multifunctional folate receptor-targeting and pH-responsive nanocarriers loaded with methotrexate for treatment of rheumatoid arthritis
title_fullStr	Multifunctional folate receptor-targeting and pH-responsive nanocarriers loaded with methotrexate for treatment of rheumatoid arthritis
title_full_unstemmed	Multifunctional folate receptor-targeting and pH-responsive nanocarriers loaded with methotrexate for treatment of rheumatoid arthritis
title_sort	multifunctional folate receptor-targeting and ph-responsive nanocarriers loaded with methotrexate for treatment of rheumatoid arthritis
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/e8fed8cfbfba4a26ae08766c2383c425
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Multifunctional folate receptor-targeting and pH-responsive nanocarriers loaded with methotrexate for treatment of rheumatoid arthritis

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