Cargando…

Intra-articular delivery of celastrol by hollow mesoporous silica nanoparticles for pH-sensitive anti-inflammatory therapy against knee osteoarthritis

BACKGROUND: Celastrol has been proven effective in anti-inflammatory but was limited in the clinic due to the poor solubility and side effects induced by low bioavailability. Osteoarthritis has acidic and inflammatory environment. Our aim was to load celastrol into HMSNs and capped with chitosan to...

Descripción completa

Detalles Bibliográficos
Autores principales: Jin, Tian, Wu, Di, Liu, Xiao-Ming, Xu, Jiang-Tao, Ma, Bing-Jie, Ji, Yun, Jin, Yu-Ying, Wu, Si-Yin, Wu, Tao, Ma, Ke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346635/
https://www.ncbi.nlm.nih.gov/pubmed/32641147
http://dx.doi.org/10.1186/s12951-020-00651-0
_version_ 1783556436822851584
author Jin, Tian
Wu, Di
Liu, Xiao-Ming
Xu, Jiang-Tao
Ma, Bing-Jie
Ji, Yun
Jin, Yu-Ying
Wu, Si-Yin
Wu, Tao
Ma, Ke
author_facet Jin, Tian
Wu, Di
Liu, Xiao-Ming
Xu, Jiang-Tao
Ma, Bing-Jie
Ji, Yun
Jin, Yu-Ying
Wu, Si-Yin
Wu, Tao
Ma, Ke
author_sort Jin, Tian
collection PubMed
description BACKGROUND: Celastrol has been proven effective in anti-inflammatory but was limited in the clinic due to the poor solubility and side effects induced by low bioavailability. Osteoarthritis has acidic and inflammatory environment. Our aim was to load celastrol into HMSNs and capped with chitosan to construct a pH-responsive nanoparticle medicine (CSL@HMSNs-Cs), which is of high solubility for osteoarthritis intra-articular injection treatment. METHODS: The CSL@HMSNs-Cs were assembled and the characteristics were measured. The CSL@HMSNs-Cs was applied in vitro in the chondrocytes collected from rats cartilage tissue and in vivo in the MIA induced knee osteoarthritis rats via intra-articular injection. Cytotoxicity assay, pH-responsive release, pain behavior, MRI, safranin o fast green staining, ELISA and western blot analysis were applied to evaluate the bioavailability and therapeutic effect of CSL@HMSNs-Cs. RESULTS: CSL@HMSNs-Cs was stable due to the protection of the chitosan layers in alkaline environment (pH = 7.7) but revealed good solubility and therapeutic effect in acidic environment (pH = 6.0). The cytotoxicity assay showed no cytotoxicity at relatively low concentration (200 μg/mL) and the cell viability of chondrocytes stimulated by IL-1β was increased in CSL@HMSNs-Cs group. Paw withdrawal threshold in CSL@HMSNs-Cs group is increased, and MRI and Safranin O Fast Green staining showed improvements in articular surface erosion and joint effusion. The upregulated expression levels of IL-1β, TNF-α, IL-6, MMP-3 and MMP-13 and NF-κB signaling pathway of chondrocytes were inhibited in CSL@HMSNs-Cs group. CONCLUSION: Hollow mesoporous silica nanoparticles were an ideal carrier for natural drugs with poor solubility and were of high biocompatibility for intra-articular injection. These intra-articular injectable CSL@HMSNs-Cs with improved solubility, present a pH-responsive therapeutic strategy against osteoarthritis.
format Online
Article
Text
id pubmed-7346635
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-73466352020-07-14 Intra-articular delivery of celastrol by hollow mesoporous silica nanoparticles for pH-sensitive anti-inflammatory therapy against knee osteoarthritis Jin, Tian Wu, Di Liu, Xiao-Ming Xu, Jiang-Tao Ma, Bing-Jie Ji, Yun Jin, Yu-Ying Wu, Si-Yin Wu, Tao Ma, Ke J Nanobiotechnology Research BACKGROUND: Celastrol has been proven effective in anti-inflammatory but was limited in the clinic due to the poor solubility and side effects induced by low bioavailability. Osteoarthritis has acidic and inflammatory environment. Our aim was to load celastrol into HMSNs and capped with chitosan to construct a pH-responsive nanoparticle medicine (CSL@HMSNs-Cs), which is of high solubility for osteoarthritis intra-articular injection treatment. METHODS: The CSL@HMSNs-Cs were assembled and the characteristics were measured. The CSL@HMSNs-Cs was applied in vitro in the chondrocytes collected from rats cartilage tissue and in vivo in the MIA induced knee osteoarthritis rats via intra-articular injection. Cytotoxicity assay, pH-responsive release, pain behavior, MRI, safranin o fast green staining, ELISA and western blot analysis were applied to evaluate the bioavailability and therapeutic effect of CSL@HMSNs-Cs. RESULTS: CSL@HMSNs-Cs was stable due to the protection of the chitosan layers in alkaline environment (pH = 7.7) but revealed good solubility and therapeutic effect in acidic environment (pH = 6.0). The cytotoxicity assay showed no cytotoxicity at relatively low concentration (200 μg/mL) and the cell viability of chondrocytes stimulated by IL-1β was increased in CSL@HMSNs-Cs group. Paw withdrawal threshold in CSL@HMSNs-Cs group is increased, and MRI and Safranin O Fast Green staining showed improvements in articular surface erosion and joint effusion. The upregulated expression levels of IL-1β, TNF-α, IL-6, MMP-3 and MMP-13 and NF-κB signaling pathway of chondrocytes were inhibited in CSL@HMSNs-Cs group. CONCLUSION: Hollow mesoporous silica nanoparticles were an ideal carrier for natural drugs with poor solubility and were of high biocompatibility for intra-articular injection. These intra-articular injectable CSL@HMSNs-Cs with improved solubility, present a pH-responsive therapeutic strategy against osteoarthritis. BioMed Central 2020-07-08 /pmc/articles/PMC7346635/ /pubmed/32641147 http://dx.doi.org/10.1186/s12951-020-00651-0 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Jin, Tian
Wu, Di
Liu, Xiao-Ming
Xu, Jiang-Tao
Ma, Bing-Jie
Ji, Yun
Jin, Yu-Ying
Wu, Si-Yin
Wu, Tao
Ma, Ke
Intra-articular delivery of celastrol by hollow mesoporous silica nanoparticles for pH-sensitive anti-inflammatory therapy against knee osteoarthritis
title Intra-articular delivery of celastrol by hollow mesoporous silica nanoparticles for pH-sensitive anti-inflammatory therapy against knee osteoarthritis
title_full Intra-articular delivery of celastrol by hollow mesoporous silica nanoparticles for pH-sensitive anti-inflammatory therapy against knee osteoarthritis
title_fullStr Intra-articular delivery of celastrol by hollow mesoporous silica nanoparticles for pH-sensitive anti-inflammatory therapy against knee osteoarthritis
title_full_unstemmed Intra-articular delivery of celastrol by hollow mesoporous silica nanoparticles for pH-sensitive anti-inflammatory therapy against knee osteoarthritis
title_short Intra-articular delivery of celastrol by hollow mesoporous silica nanoparticles for pH-sensitive anti-inflammatory therapy against knee osteoarthritis
title_sort intra-articular delivery of celastrol by hollow mesoporous silica nanoparticles for ph-sensitive anti-inflammatory therapy against knee osteoarthritis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346635/
https://www.ncbi.nlm.nih.gov/pubmed/32641147
http://dx.doi.org/10.1186/s12951-020-00651-0
work_keys_str_mv AT jintian intraarticulardeliveryofcelastrolbyhollowmesoporoussilicananoparticlesforphsensitiveantiinflammatorytherapyagainstkneeosteoarthritis
AT wudi intraarticulardeliveryofcelastrolbyhollowmesoporoussilicananoparticlesforphsensitiveantiinflammatorytherapyagainstkneeosteoarthritis
AT liuxiaoming intraarticulardeliveryofcelastrolbyhollowmesoporoussilicananoparticlesforphsensitiveantiinflammatorytherapyagainstkneeosteoarthritis
AT xujiangtao intraarticulardeliveryofcelastrolbyhollowmesoporoussilicananoparticlesforphsensitiveantiinflammatorytherapyagainstkneeosteoarthritis
AT mabingjie intraarticulardeliveryofcelastrolbyhollowmesoporoussilicananoparticlesforphsensitiveantiinflammatorytherapyagainstkneeosteoarthritis
AT jiyun intraarticulardeliveryofcelastrolbyhollowmesoporoussilicananoparticlesforphsensitiveantiinflammatorytherapyagainstkneeosteoarthritis
AT jinyuying intraarticulardeliveryofcelastrolbyhollowmesoporoussilicananoparticlesforphsensitiveantiinflammatorytherapyagainstkneeosteoarthritis
AT wusiyin intraarticulardeliveryofcelastrolbyhollowmesoporoussilicananoparticlesforphsensitiveantiinflammatorytherapyagainstkneeosteoarthritis
AT wutao intraarticulardeliveryofcelastrolbyhollowmesoporoussilicananoparticlesforphsensitiveantiinflammatorytherapyagainstkneeosteoarthritis
AT make intraarticulardeliveryofcelastrolbyhollowmesoporoussilicananoparticlesforphsensitiveantiinflammatorytherapyagainstkneeosteoarthritis