Akademik Veri Yönetim Sistemi
Tezin Türü: Doktora
Tezin Yürütüldüğü Kurum: Orta Doğu Teknik Üniversitesi, Mühendislik Fakültesi, Mühendislik Bilimleri Bölümü, Türkiye
Tezin Onay Tarihi: 2014
Öğrenci: AYŞEGÜL KAVAS
Eş Danışman: AYŞEN TEZCANER, DİLEK KESKİN
Özet:One of the osteoporosis drugs, Raloxifene (Ral) is systemically administrated in high dose at frequent intervals, causing high risk of side effects which influence all the body. As a solution to such issues, delivery systems providing controlled and sustained drug release at therapeutic level from a carrier have been studied recently. The aim of this study was to develop Ral- or Ral-poly(ethylene glycol) (PEG)-loaded poly(ε-caprolactone) (PCL) or PCL:poly(D,L-lactide-co-glycolide) (PLGA) microspheres and to evalute their potential usage. Mean diameters of the microspheres were around 1.5 μm. Ral-loaded PCL microspheres had maximum Ral encapsulation efficiency (%) because of high hydrophobic natures of Ral and PCL. Total amount of Ral released from Ral-PEG-loaded PCL:PLGA microspheres was significantly higher than from other microsphere groups. This finding can be ascribed to enhanced wettability of Ral and conversion of crystalline nature of Ral to amorphous form provided by Ral-PEG conjugation, resulting in increased water-solubility of Ral. Enhanced wettability of Ral increases degradation rates of PCL and PLGA by allowing more water penetration into the polymer matrix. Related with this outcome, Ral release from Ral-PEG-loaded PCL:PLGA microspheres resulted with significantly higher mineralization of female adipose-derived mesenchymal stem cells than other groups. In vitro cytotoxicity studies performed using adipose-derived stem cells demonstrated that all microspheres were non-toxic. It was demonstrated that Ral-PEG-loaded PCL:PLGA microsphere formulation provided increased Ral release rate and therefore enhanced mineralization of the stem cells compared to the other formulations in this study. This formulation holds promise for osteoporosis therapy as an effective controlled drug delivery system. For forthcoming studies, PEG conjugation to Ral presents the possibility of adjusting rate of Ral release from microspheres readily by changing PEG ratio in the conjugate.