Akademik Veri Yönetim Sistemi
Tezin Türü: Doktora
Tezin Yürütüldüğü Kurum: Orta Doğu Teknik Üniversitesi, Mühendislik Fakültesi, Mühendislik Bilimleri Bölümü, Türkiye
Tezin Onay Tarihi: 2013
Öğrenci: ÖZGE ERDEMLİ
Danışman: AYŞEN TEZCANER
Özet: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.