Development Of Pcl-Based Membranes By Usıng Electrospınnıng Method For Drug Delıvery Systems


Thesis Type: Doctorate

Institution Of The Thesis: Gazi Üniversitesi, Fen Bilimleri Enstitüsü, Turkey

Approval Date: 2018

Student: ŞÜKRAN MELDA ESKİTOROS TOĞAY

Supervisor: NURSEL DİLSİZ

Abstract:

The purpose of this thesis is to develop nano/microfiber membranes produced by electrospinning method in order to be used as drug delivery vehicles, and to investigate in vitro activity of two different model drugs. The first model drug used in this study is quercetin which is widely found in nature and a member of the flavonol group. For the production of a quercetin delivery membrane, firstly drug-unloaded membranes were produced from the polymer mixtures of polycaprolactone/polyethylene oxide, polycaprolactone/polylactic-co-glycolide acid and polycaprolactone/polylactic acid. Quercetin was then added to these three membranes at a ratio of 20% (w/w) and only 4% (w/w) to the polymer mixture of polycaprolactone/polyethylene oxide, and the production of drug-loaded nano/micro fiber membranes was performed by electrospinning method. According to the characterization, in vitro release and cytotoxicity studies, polycaprolactone/polyethylene oxide mixture was found as an ideal drug delivery system for the release studies of quercetin having lower water solubility. Another model drug is chosen as doxycycline, which has a high water solubility and a broad-spectrum antibiotic from the tetracycline family. For the doxycycline delivery systems, doxycycline was first loaded at a ratio of 3.5% (w/w) to the polycaprolactone/polyethylene oxide polymer blends of 100:0, 75:25, 50:50, 25:75, 0:100 (w/w). According to the characterization and in vitro release studies, it was decided that the membrane obtained from the polymer mixture of polycaprolactone/polyethylene oxide at the ratio of 75:25 (w/w) is the most suitable vehicle for doxycycline. Therefore, doxycycline loaded 75:25 (w/w) polycaprolactone/polyethylene oxide membranes at different ratios (2%, 5%, 7%, 14% and 21% w/w) were produced by electrospinning method. It was found that the drug release increased by increasing the amount of drug loaded in the membranes; however, the release was obtained as a burst release. Thus, three different core-shell membranes loading with 3.5% (w/w) doxycycline were produced by electrospinning method with co-axial nozzle system for controlled release. In vitro release studies showed that drug release was obtained more controlled than the membranes synthesized by uniaxial electrospinning.