Anti-TNF Kontrollü Salım Sisteminin Romatoid Artirit Tedavilerine Yönelik Etkilerinin Hücre Kültüründe İncelenmesi

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2012

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Özen, Seza
Tezcaner, Ayşen
Keskin, Dilek Esra
Usanmaz, Ali
Atilla, Bülent

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Anti-TNFα drugs for rheumatoid arthritis treatment show comprehensive effect against inflammation with their ability to reduce significantly TNFα and other proinflammatory cytokine production. However, there are some restrictions for anti-TNFα treatment because of long-term usage and toxic effects. Intraarticularly injectable polycaprolactone (PCL) and PEGylated polycaprolactone (PEGPCL-PEG) microspheres releasing anti-TNFα for more than 3 months, were prepared and their effectiveness in treatment were examined with in vitro studies. PEG-PCL-PEG was synthesized from PEG-PCL diblock copolymer using coupling agent. Immunoglobulin G was used to for optimization studies. Particle size of anti-TNFα loaded PCL and PEG-PCL-PEG microspheres was 5 μm and microspheres had high encapsulation efficiencies (65.37 ± 1.80 % and 75.91 ± 1.16 %, respectively). Biologically active drug release during 3 months was observed for each group. Anti-TNFα loaded microspheres and free anti-TNFα were incubated with synoviocytes isolated from RA patients for 1 month and time-dependent changes in the quantity and mRNA expression levels of the proinflomatory cytokines (TNF-α, IL-6, IL-17 ve IFN-γ) and matrix metalloproteases (MMP) 3 and 13 were investigated by ELISA and PCR methods. Levels of cytokines and MMPs released from synoviocytes incubated with anti-TNFα loaded microspheres were significantly lower than that of released free anti-TNFα group.MMP-3 and IL6 gene expressions of synoviocytes incubated with microspheres were upregulated at week2 whereas MMP-13 gene of synoviocytes incubated with free drug was upregulated at week3. At other time points, no change was observed. According to the results, potential usage of PCL and PEG-PCL-PEG controlled release systems in clinical applications is high

Subject Keywords

Romatoid Arthritis, Anti-TNF, Poly(caprolactone), Pegylated poly(captolactone), Microsphere, Controlled release systems

URI

https://app.trdizin.gov.tr/publication/project/detail/TVRVNE9URXg
https://hdl.handle.net/11511/49932

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Graduate School of Natural and Applied Sciences, Project and Design

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Citation Formats

S. Özen, A. Tezcaner, D. E. Keskin, A. Usanmaz, and B. Atilla, “Anti-TNF Kontrollü Salım Sisteminin Romatoid Artirit Tedavilerine Yönelik Etkilerinin Hücre Kültüründe İncelenmesi,” 2012. Accessed: 00, 2020. [Online]. Available: https://app.trdizin.gov.tr/publication/project/detail/TVRVNE9URXg.