Matriks metalloproteinaz inhibitörü etkili ilaç taşıyan salım sisteminin kıkırdak hastalıkları tedavisindeki etkinliğinin incelenmesi

TÜBİTAK TBAG Proje01.08.201

Osteoartiritte Matriks Proteinlerinin Gen Ekspresyonuna Raloksifenin Etkisi

Bu projede Ral'in osteoartiritli hücrelerde matriks proteinleri gen ekspresyonuna etkilerinin incelenmesi ile OA tedavi potansiyelinin araştırılması amaçlanmıştır. Östrojen reseptörlerini modüle etmesi nedeniyle yan etkileri çok fazla olan östrojen yerine osteoporoz tedavisinde tercih edilen temel bir ilaç olan raloksifenin klinik uygulamalar sonucunda tesadüfi olarak OA üzerinde olumlu etkisi bulunması kıkırdak hasarlarının tedavisinde yeni- farklı bir ajanın kullanılabilirliği sonucunu getirmiştir. Bu proje ile etkileri daha çok klinik ve kıkırdak matriks oluşumu olarak macromoleküler düzeyde araştırılmış olan bu ajanın moleküler düzeyde kıkırdak hasarında-iyileşmesinde farklı dozlarda nasıl bir rolü olduğu konusunda literatüre önemli bilgi sağlanacağı düşünülmektedi

Tissue engineered retinal pigment epithelium

Ph.D. - Doctoral Progra

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

FEN BİLİMLERİ ENSTİTÜSÜ/LİSANSÜSTÜ TEZ PROJESİ

YAĞ DOKUSUNDAN HÜCRE UZAKLAŞTIRMA İLE ELDE EDİLEN HÜCRE DIŞI MATRİKS İLE RAT MODELİNDE DAMARLI ADİPOZ DOKU KONSTRÜKSÜ GELİŞTİRİLMES

Klinoptilolit /Poli ε-kaprolakton - Poli etilen glikol - Poli ε-kaprolakton (PCL-PEG-PCL) Triblok Kopolimer Temelli Hücre Taşıyıcıların Geliştirilmesi ve Karakterizasyonu

Hafif travma ve zedelenme geçirmiş kemik dokusu konvensiyonel yöntemler ile kolayca tedavi edilebilmektedirler. Ancak, ağır travma ve/veya kompleks kırıklar sonucunda oluşmuş olan kemik dokusu hasarlarının tedavisinde, kemik dokusunun rejenerasyonuna yardımcı olarak hücre taşıyıcıların desteğine gerek duyulmaktadır. Son yıllarda, kemik hasarlarının giderilmesinde polimer bazlı kompozit hücre taşıyıcılar sıklıkla kullanılmaktadır. Bu biyouyumlu ve mekanik olarak güçlü polimer bazlı kompozit hücre taşıyıcılar, hücrelerin kemikteki travma bölgesine daha hızlı ve etkin bir şekilde taşınması sağlamaktadır. Önerilen projede, kemik iyileşmesini arttırmak için kemik siyaloprotein ile kaplanmış klinoptilolit/poli ε-kaprolakton- poli etilen glikol- poli ε-kaprolakton (PCL-PEG-PCL) temelli gözenekli hücre taşıyıcıların geliştirilmesi ve biyomalzeme özelliklerinin incelenmesi amaçlanmaktadır. Projede, kemik doku mühendisliğine yönelik, biyobozunur, biyouyumlu, mekanik dayanımı yüksek ve protein bazlı biyoaktif faktörlerin yüklenebileceği gözenekli hücre taşıyıcıların geliştirilmesi hedeflenmiştir. Ayrıca, geliştirilecek hücre taşıyıcısının yapısında bulunan zeolit mineralinin bir türü olan klinoptilolitin iyonik yapısı sayesinde kemik siyaloproteinin yüksek etkinlikte hücre taşıyıcısına yüklenebilmesini ve kontrollü salımını sağlayacağı düşünülmektedir. Literatürde de belirtildiği gibi, zeolit mineralleri iyonik yapılarından dolayı protein yapısındaki faktörleri kendi yapılarına dah

FEN BİLİMLERİ ENSTİTÜSÜ/LİSANSÜSTÜ TEZ PROJESİ

KEMİK DOKU MÜHENDİSLİĞİ İÇİN HİDROKSİAPATİT/FİBROİN MİKROKÜRELE

Micelles As Delivery System for Cancer Treatment

Micelles are nanoparticles formed by the self-assembly of amphiphilic block copolymers in certain solvents above concentrations called critical micelle concentration (CMC). Micelles are used in different fields like food, cosmetics, medicine, etc. These nanosized delivery systems are under spotlight in the recent years with new achievements in terms of their in vivo stability, ability to protect entrapped drug, release kinetics, ease of cellular penetration and thereby increased therapeutic efficacy. Drug loaded micelles can be prepared by dialysis, oil-in-water method, solid dispersion, freezing, spray drying, etc. The aim of this review is to give an overview of the research on micelles (in vitro, in vivo and clinical) as delivery system for cancer treatment. Passive targeting is one route for accumulation of nanosized micellar drug formulations. Many research groups from both academia and industry focus on developing new strategies for improving the therapeutic efficacy of micellar systems (active targeting to the tumor site, designing multidrug delivery systems for overcoming multidrug resistance or micelles formed by prodrug conjugates, etc). There is only one micellar drug formulation in South Korea that has reached clinical practice. However, there are many untargeted anticancer drug loaded micellar formulations in clinical trials, which have potential for use in clinics. Many more products are expected to be on the market in the near future

In vitro characterization of micropatterned PLGA-PHBV8 blend films as temporary scaffolds for photoreceptor cells

In developed countries the aging population faces increasing risks of blinding retinal diseases, for which there are few effective treatments available. Photoreceptor transplantation represents one approach, but generally results have been disappointing. We hypothesize that micropatterned biodegradable poly(L-lactic acid-co-glycolic acid) /poly(hydroxybutyrate-co-hydroxyvaleric acid) (PLGA-PHBV8) blend films could deliver photoreceptor cells in a more organized manner than bolus injections. Blending of PLGA and PHBV8 was used to optimize the degradation rate of the temporary template. At the end of 8 weeks, for both thin and thick films of PLGA-PHBV8 a 50% decrease of their initial weight with increasing water uptake was observed. When photoreceptor cells were seeded onto micropatterned PLGA-PHBV8 films with parallel grooves (21- and 42-mu m-wide grooves and 20 mu m ridge width and depth), the cells preferred laminin-deposited grooves to ridges and expressed rod- and cone-specific markers such as rhodopsin and arrestin. A loss in photoreceptor viability of 50% was observed after 7 days in culture. The effects of either retinal pigment epithelium (RPE)-derived or Muller glial cell-derived conditioned media or bFGF on the survival of photoreceptor cells seeded on PLGA-PHBV8 films were investigated. Addition of either RPE- and Muller-conditioned media increased statistically (p < 0.01) the viability of photoreceptor cells after 7 days of incubation. Our results suggest that such biodegradable micropatterned PLGA-PHBV8 blend films have a potential to deliver photoreceptor cells to the subretinal space and ensure laminar organization and maintenance of differentiation, and that incorporation of intrinsic factors within the scaffold would enhance the survival rate of transplanted cells. (C) 2007 Wiley Periodicals, Inc