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

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 drug...

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Autores principales: Zhao, Jinlong, Zhao, Menghui, Yu, Changhui, Zhang, Xueyan, Liu, Jiaxin, Cheng, Xinwei, Lee, Robert J, Sun, Fengying, Teng, Lesheng, Li, Youxin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5600269/
https://www.ncbi.nlm.nih.gov/pubmed/28932117
http://dx.doi.org/10.2147/IJN.S140992
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author Zhao, Jinlong
Zhao, Menghui
Yu, Changhui
Zhang, Xueyan
Liu, Jiaxin
Cheng, Xinwei
Lee, Robert J
Sun, Fengying
Teng, Lesheng
Li, Youxin
author_facet Zhao, Jinlong
Zhao, Menghui
Yu, Changhui
Zhang, Xueyan
Liu, Jiaxin
Cheng, Xinwei
Lee, Robert J
Sun, Fengying
Teng, Lesheng
Li, Youxin
author_sort Zhao, Jinlong
collection PubMed
description 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.
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spelling pubmed-56002692017-09-20 Multifunctional folate receptor-targeting and pH-responsive nanocarriers loaded with methotrexate for treatment of rheumatoid arthritis Zhao, Jinlong Zhao, Menghui Yu, Changhui Zhang, Xueyan Liu, Jiaxin Cheng, Xinwei Lee, Robert J Sun, Fengying Teng, Lesheng Li, Youxin Int J Nanomedicine Original Research 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. Dove Medical Press 2017-09-11 /pmc/articles/PMC5600269/ /pubmed/28932117 http://dx.doi.org/10.2147/IJN.S140992 Text en © 2017 Zhao et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Zhao, Jinlong
Zhao, Menghui
Yu, Changhui
Zhang, Xueyan
Liu, Jiaxin
Cheng, Xinwei
Lee, Robert J
Sun, Fengying
Teng, Lesheng
Li, Youxin
Multifunctional folate receptor-targeting and pH-responsive nanocarriers loaded with methotrexate for treatment of rheumatoid arthritis
title 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_short 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
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5600269/
https://www.ncbi.nlm.nih.gov/pubmed/28932117
http://dx.doi.org/10.2147/IJN.S140992
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