Darunavir Baskılanmış Phema Temelli Mikrokriyojellerin Hazırlanması ve Salım Kinetiğinin İncelenmesi
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Darunavir (D.V) is a powerful Antiretroviral drug used to treat infections with the human immunodeficiency virus (HIV). Acquired immunodeficiency syndrome (AIDS) is the most advanced stage of HIV infection. D.V is a synthetic non-peptide protease inhibitor that was first approved by the FDA for resistant type-1 treatment of HIV, in June 2006. Controlled drug release systems offer an effective treatment method by using drugs to the target tissue at the specific dose, at the right time, and place during the treatment of diseases. Polymeric systems as biomaterials are used in controlled release systems that can be obtained naturally/synthetically. The use of these materials is increasing nowadays. One of these biomaterials is microcryogels, which are derivatives of hydrogels, and gel matrices synthesized under the freezing temperature of the solvent. Since microcryogels have supermacroporosity, elastic and spongy morphology, they have recently been used in biomedical applications such as drug release. In this thesis study, the controlled release and kinetic studies of darunavir were investigated with the D.V imprinted poly (2-hydroxyethyl methacrylate) (PHEMA) based microcryogels. Darunavir imprinted PHEMA microcryogels with different crosslinker ratios and different loaded drug were prepared for in vitro release studies of darunavir. In the first step, the MAH monomer was complexed with Cu (II) metal ions at three different molar ratios. Then, darunavir imprinted microcryogels were prepared at -14oC. In the second stage, the structure and surface morphology of microcryogels were characterized with FTIR-ATR, scanning electron microscopy (SEM), swelling experiments and surface area measurements. According to the SEM results, it was observed that the microcryogels were homogeneously distributed with macroporous sizes greater than 20 µm. Also, the surface area and % swelling of microcryogels were increased by increasing the amount of loaded darunavir. In the third stage, the effect of different Cu (II) ion, drug loaded amount, crosslinker and pH on in vitro D.V release rate was investigated. Different D.V imprinted microcryogels were prepared by loading different amounts of darunavir (0.5-1.75 mg/mL). It was demosntarted that D.V release rate was increased by increasing the amount of D.V. Also, darunavir imprinted microcryogels were prepared in three different mole ratios of MBAAm (nHEMA/nMBAAm = 4, 6, 8), as crosslinker. The controlled release of D.V. was decreased by increasing the crosslinker density. The release of darunavir from drug imprinted microcryogels at different pH (6.0, 7.0, 7.4, and 8.0) was studied. According to the results, the most and controlled drug release was occured at pH 7.4. Finally, cytotoxicity studies of the microcryogels were performed using the fibroblast cell line (L929) in the thesis study.