Show/Hide Menu
Hide/Show Apps
Logout
Türkçe
Türkçe
Search
Search
Login
Login
OpenMETU
OpenMETU
About
About
Open Science Policy
Open Science Policy
Open Access Guideline
Open Access Guideline
Postgraduate Thesis Guideline
Postgraduate Thesis Guideline
Communities & Collections
Communities & Collections
Help
Help
Frequently Asked Questions
Frequently Asked Questions
Guides
Guides
Thesis submission
Thesis submission
MS without thesis term project submission
MS without thesis term project submission
Publication submission with DOI
Publication submission with DOI
Publication submission
Publication submission
Supporting Information
Supporting Information
General Information
General Information
Copyright, Embargo and License
Copyright, Embargo and License
Contact us
Contact us
Development of novel controlled release formulations of anti-tnf for rheumatoid arthritis and modeling of release behaviors
Download
index.pdf
Date
2013
Author
Erdemli, Özge
Metadata
Show full item record
Item Usage Stats
335
views
130
downloads
Cite This
Anti-TNFα drugs are widely used in treatment of rheumatoid arthritis. However, long term use of these drugs involves systemic effects. New era in medication involves controlled delivery systems that will provide local sustained release of drug. This study aims to develop a novel intra-articularly injectable etanercept (ETN) loaded poly(ε-caprolactone) (PCL) or methoxypoly(ethyleneglycol)-poly(ε-caprolactone)-methoxypoly(ethyleneglycol) (MPEG-PCL-MPEG) microspheres (patent pending) for the treatment of chronic inflammatory arthritides (CIA). MPEG-PCL-MPEG was synthesized by ring-opening polymerization. Immunoglobulin G (IgG) was used as a model protein for optimization of microsphere preparation. MPEG-PCL-MPEG microspheres had higher encapsulation efficiency than PCL ones for both IgG and ETN. Presence of MPEG was found to have protective effect on loaded and released protein. Microspheres had mean particle sizes around 5 μm. Total amounts of biologically active protein released from MPEG-PCL-MPEG microspheres were significantly higher than from PCL microspheres. ETN release mechanism obeyed to anomalous transport in PBS and in cell culture medium whereas it followed Fickian diffusion in synovial fluid. Sustained ETN release from microspheres resulted with a significant decrease in pro-inflammatory cytokines and matrix metalloproteinase levels, while conserving viability of fibroblast-like synovial cells (FLS) compared to free drug. There was no significant variation in the gene expressions among groups. vi This study showed that presence of MPEG improved the properties of PCL microspheres as delivery system by providing higher ETN stability, release and encapsulation efficiency, besides improving the degradation properties and increasing hydrophilicity, and thus biocompatibility. MPEG-PCL-MPEG and PCL microspheres are promising systems for an effective local treatment approach in CIA.
Subject Keywords
Arthritis.
,
Rheumatoid arthritis.
URI
http://etd.lib.metu.edu.tr/upload/12616193/index.pdf
https://hdl.handle.net/11511/22844
Collections
Graduate School of Natural and Applied Sciences, Thesis
Suggestions
OpenMETU
Core
In vitro evaluation of effects of sustained anti-TNF release from MPEG-PCL-MPEG and PCL microspheres on human rheumatoid arthritis synoviocytes
Erdemli, Ozge; Özen, Seza; Keskin, Dilek; Usanmaz, Ali; Batu, Ezgi Deniz; Atilla, Bülent; Tezcaner, Ayşen (2014-10-01)
Anti-tumor necrosis factor (TNF) drugs such as etanercept (ETN) have been mostly used in systemic treatment of rheumatoid arthritis. To eliminate the side effects in long-term treatments and to achieve a local sustained anti-inflammatory effect, a controlled drug delivery system is needed for anti-TNF drugs. This study aims to develop novel injectable microcarriers of ETN that can provide long-term controlled release of this protein drug upon intra-articular application. In this study, poly(epsilon-caprolac...
Variables related to posttraumatic growth in Turkish rheumatoid arthritis patients
Dirik, Gulay; Karancı, Ayşe Nuray (2008-09-01)
Rheumatoid arthritis (RA) is a chronic, deteriorative disease, which can cause great psychological distress. Although RA has negative psychological consequences, it may also lead to positive changes, which has been given relatively little attention in the research literature. The Posttraumatic Growth Inventory (PTGI) has been used to evaluate growth in survivor's thinking, feeling and/or behavior following the experiencing of traumatic or severely adverse life events. The purpose of the current study was to...
Psychological distress in rheumatoid arthritis patients: An evaluation within the conservation of resources theory
Dirik, Gulay; Karancı, Ayşe Nuray (2010-01-01)
Rheumatoid arthritis (RA) is a chronic disease, which can lead to considerable psychological distress. The present study evaluated anxiety and depression symptoms for this chronic and painful illness within the framework of the conservation of resources (COR) theory. Coping strategies, coping self-efficacy, religiousness and social support are very important personal resources, which have been found to protect individuals from psychological distress. The aim of the present study was to examine the predictiv...
Characterization and Evaluation of Triamcinolone, Raloxifene, and Their Dual-Loaded Microspheres as Prospective Local Treatment System in Rheumatic Rat Joints
Ocal, Yigit; Kurum, Baris; Karahan, Siyami; Tezcaner, Ayşen; Ozen, Seza; Keskin, Dilek (Elsevier BV, 2014-8)
In this study, injectable microspheres were developed for the local treatment of joint degeneration in rheumatoid arthritis (RA). Microspheres loaded with triamcinolone (TA), a corticosteroid drug, and/or raloxifene (Ral), a cartilage regenerative drug, were prepared with a biodegradable and biocompatible polymer, polycaprolactone (PCL). Microspheres were optimized for particle size, structural properties, drug release, and loading properties. In vitro release of Ral was very slow because of the low solubil...
Structural effects of simvastatin on liver rate tissue: Fourier transform infrared and Raman microspectroscopic studies
Garip, Sebnem; Bayari, Sevgi Haman; Severcan, Mete; Abbas, Sherif; Lednev, Igor K.; Severcan, Feride (2016-02-01)
Simvastatin is one of the most frequently prescribed statins because of its efficacy in the treatment of hypercholesterolemia, reducing cardiovascular risk and related mortality. Determination of its side effects on different tissues is mandatory to improve safe use of this drug. In the present study, the effects of simvastatin on molecular composition and structure of healthy rat livers were investigated by Fourier transform infrared and Raman imaging. Simvastatin-treated groups received 50 mg/kg/day simva...
Citation Formats
IEEE
ACM
APA
CHICAGO
MLA
BibTeX
Ö. Erdemli, “Development of novel controlled release formulations of anti-tnf for rheumatoid arthritis and modeling of release behaviors,” Ph.D. - Doctoral Program, Middle East Technical University, 2013.
