Intra-articular delivery of celastrol by hollow mesoporous silica nanoparticles for pH-sensitive anti-inflammatory therapy against knee osteoarthritis
Abstract 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 chit...
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| Format: | Article |
| Language: | English |
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BMC
2020-07-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | http://link.springer.com/article/10.1186/s12951-020-00651-0 |
| _version_ | 1798041276848799744 |
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| author | Tian Jin Di Wu Xiao-Ming Liu Jiang-Tao Xu Bing-Jie Ma Yun Ji Yu-Ying Jin Si-Yin Wu Tao Wu Ke Ma |
| author_facet | Tian Jin Di Wu Xiao-Ming Liu Jiang-Tao Xu Bing-Jie Ma Yun Ji Yu-Ying Jin Si-Yin Wu Tao Wu Ke Ma |
| author_sort | Tian Jin |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-11T22:19:16Z |
| format | Article |
| id | doaj.art-8715cb88a3e547869dc574e2efb45018 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-11T22:19:16Z |
| publishDate | 2020-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-8715cb88a3e547869dc574e2efb450182022-12-22T04:00:16ZengBMCJournal of Nanobiotechnology1477-31552020-07-0118111510.1186/s12951-020-00651-0Intra-articular delivery of celastrol by hollow mesoporous silica nanoparticles for pH-sensitive anti-inflammatory therapy against knee osteoarthritisTian Jin0Di Wu1Xiao-Ming Liu2Jiang-Tao Xu3Bing-Jie Ma4Yun Ji5Yu-Ying Jin6Si-Yin Wu7Tao Wu8Ke Ma9Department of Pain Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineDepartment of Urology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineDepartment of Pain Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineDepartment of Pain Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineDepartment of Pain Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineDepartment of Pain Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineDepartment of Pain Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineDepartment of Pain Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai Jiao Tong University School of MedicineDepartment of Pain Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineAbstract 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.http://link.springer.com/article/10.1186/s12951-020-00651-0CelastrolHollow mesoporous silica nanoparticleOsteoarthritisIntra-articular injectionpH-responsive |
| spellingShingle | Tian Jin Di Wu Xiao-Ming Liu Jiang-Tao Xu Bing-Jie Ma Yun Ji Yu-Ying Jin Si-Yin Wu Tao Wu Ke Ma Intra-articular delivery of celastrol by hollow mesoporous silica nanoparticles for pH-sensitive anti-inflammatory therapy against knee osteoarthritis Journal of Nanobiotechnology Celastrol Hollow mesoporous silica nanoparticle Osteoarthritis Intra-articular injection pH-responsive |
| 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 | Celastrol Hollow mesoporous silica nanoparticle Osteoarthritis Intra-articular injection pH-responsive |
| url | http://link.springer.com/article/10.1186/s12951-020-00651-0 |
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