MCM-41 mezogözenekli silika parçacıklarına selekoksib yükleme çalışmaları: ilaç yükleme ve bırakma özellikleri.


Tezin Türü: Yüksek Lisans

Tezin Yürütüldüğü Kurum: Orta Doğu Teknik Üniversitesi, Fen Edebiyat Fakültesi, Kimya Bölümü, Türkiye

Tezin Onay Tarihi: 2014

Tezin Dili: İngilizce

Öğrenci: Şahika Günaydin

Danışman: AYŞEN YILMAZ

Özet:

Mesoporous silica particles have been used to enhance the biocompability of the drugs and provide control drug release. Celecoxib was chosen as a model drug which is poorly water soluble non-steroidal anti-inflammatory drug. In this study, in order to determine the morphology effect on the drug loading capacity of the silica particles and release properties of the drug, MCM-41 particles were synthesized with different particle size, pore volume and surface properties. MCM-41-1 and MCM-41-2 labeled particles were nearly 50 nm with spherical shape and MCM-41-3 had ellipsoidal shape with nearly 500 nm particle diameter. In order to observe the template removal process on morphology of samples, acid extraction and calcination were performed. Boron doping of MCM-41 samples was prepared and borosilicate samples were obtained. Surfaces of samples were functionalized by post – grafting method with three different functional groups to observe the behavior of unfunctionalized and functionalized surfaces. Polyethylene glycol (PEG), luminescent groups and (3-Aminopropyl) triethoxysilane (APTES) were used in this way. Drug loading was examined in three different solvents, methanol, ethanol and vi hexane, to observe the effect of polarity of solvent on the drug loading capacity of the carrier particles. For the characterization process of pure and drug loaded samples, X-ray Diffraction (XRD), N2 adsorption - desorption, Fourier Transform Infra-red (FTIR), Elemental Analysis, Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Ultra-Violet Spectrometry (UV-VIS), Zeta Potential and Thermogravimetric Analysis (TGA) were applied. According to characterization process, Celecoxib remained in crystalline state in hexane and MCM-41-1 silica particles with highest pore volume held the highest amount of Celecoxib in it (29.51% by wt/wt). However, drug molecules were finely dispersed in ethanol and carrier particles held 25.95% Celecoxib in their pores and channels. It has been seen that functionalization could not increase the drug loading capacity of the MCM-41 particles. The release experiments of the Celecoxib molecules in all samples were performed in phosphate buffer solution (PBS) pH=7.4 at 37 °C. Release rate of the drug molecules were also highly improved by using MCM-41 silica particles as drug carriers according to its commercial drug capsule, Celebrex. Sustained release was observed for all the samples. Celecoxib molecules loaded to carrier particles in ethanol were released faster in first six hours than hexane loaded samples. Among the silica samples, MCM-41-3 with average size released the lowest amount of drug in this time interval (63% in ethanol loaded and 59% in hexane loaded) and highest amount of release observed in borosilicate samples (87% in ethanol loaded and 66% in hexane loaded). These results confirm the potential of silica supports as drug delivery carriers for low water solubility drugs.