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Osteoporoz Tedavisine Yönelik Kemik Hedefli Plga-Pcl Nanokürelerin Hazırlanması Ve Karakterizasyonu

There are many therapeutic agents used for treatment of osteoporosis in clinics. However, most of them are not specific to bone and their use mostly gives rise to many side effects. Moreoever, there is a need for frequent systemic administration of these agents. As a solution to these issues, bone targeted drug delivery is being investigated recently. The main principle behind this strategy is that it provides controlled release of the therapeutic agent at the target site. Therefore, many side effects due to use of high dose and the administration frequency of the agent can be lowered. In this Ph.D. study, it is aimed to synthesize raloxifene loaded polymer based-nanospheres conjugated with alendronate and characterize them with in situ and in vitro studies. The hypothesis of the study is that the raloxifene loaded nanospheres conjugated with alendronate will provide targeted delivery of raloxifene to osteoporotic bone and osteogenic effect on mesenchymal stem cells in the bone that will improve effectiveness of raloxifene treatment. Until now, raloxifene loaded microspheres were prepared and characterized by scanning electron microscopy (SEM). SEM examinations showed that all the microspheres had a spherical shape and homogeneous in size distribution. Bone marrow mesenchymal stem cells were isolated from rats in order to investigate the effects of free raloxifene and raloxifene loaded microspheres on viability of the mesenchymal stem cells. In vitro cytotoxicity studies showed that raloxifene did not cause a significant loss in the viability of mesenchymal stem cells. However, incubation of mesenchymal stem cells with raloxifene loaded microspheres lowered the viability of cells. Experiments for release studies and encapsulation efficiency of the microspheres are under study. For release studies, HPLC method has been optimized and the calibration curve of raloxifene has been obtained.