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Erschienen in: Inflammopharmacology 5/2019

01.01.2019 | Original Article

Anti-inflammatory role of TPCA-1 encapsulated nanosomes in porcine chondrocytes against TNF-α stimulation

verfasst von: Fazal Ur Rehman Bhatti, Karen A. Hasty, Hongsik Cho

Erschienen in: Inflammopharmacology | Ausgabe 5/2019

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Abstract

In this study, we evaluated the hypothesis that immunonanosomes carrying the drug [5-(p-Fluorophenyl)-2-ureido]thiophene-3-carboxamide (TPCA-1) will help in reducing nuclear factor-kappaB (NF-κB)-associated inflammation in porcine chondrocytes against tumor necrosis factor-alpha (TNF-α)-induced stress. The nanosomes were tagged with monoclonal anti-type II collagen (MabCII) antibody to specifically target the exposed type II collagen in cartilage matrix. TPCA-1 at a concentration of 10 µM significantly reduced expression of the matrix-degrading enzyme, Matrix metalloproteinase-13 (MMP-13) and blocked the p65 nuclear translocation. In comparison to the TPCA-1 solution alone, the TPCA-1 nanosomes were found to be more effective in reducing the cellular toxicity, oxidative stress and inflammation in chondrocytes treated with TNF-α. In addition, TPCA-1 nanosomes were more effective in reducing the gene expression of hypoxia-inducible factor-2alpha (HIF-2α) that in turn is associated with the regulation of MMP-13 gene. TPCA-1 nanosomes significantly reduced expression of both these genes. The data also showed that TPCA-1 did not attenuate the down-regulated gene expression levels of anabolic genes aggrecan (ACAN) and collagen type II alpha (COL2A1). In conclusion, this study showed that TPCA-1 nanosomes carrying a dose of 10 µM TPCA-1 can effectively increase the survival of cultured porcine chondrocytes against TNF-α-induced stress. The findings of this study could be used to develop nanosome-based drug delivery systems (DDSs) for animal model of OA. Moreover, the approach presented here can be further utilized in other studies for targeted delivery of the drug of interest at a cellular level.
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Metadaten
Titel
Anti-inflammatory role of TPCA-1 encapsulated nanosomes in porcine chondrocytes against TNF-α stimulation
verfasst von
Fazal Ur Rehman Bhatti
Karen A. Hasty
Hongsik Cho
Publikationsdatum
01.01.2019
Verlag
Springer International Publishing
Erschienen in
Inflammopharmacology / Ausgabe 5/2019
Print ISSN: 0925-4692
Elektronische ISSN: 1568-5608
DOI
https://doi.org/10.1007/s10787-018-0542-5

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