Kemoterapötik ilaç taşıyıcı sistemler: Radyoişaretli siklofosfamid yüklü mezopor silika nanoparçacıklar
Yükleniyor...
Tarih
2020
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi, Fen Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Son yıllarda terapötik ve hedefe spesifik ilaçların taşınmasında nanoparçacıkların (NP) sağladığı imkanlar bilim insanları ve ilaç endüstrisi tarafından giderek artan ilgiyle karşılanmaktadır. Bu taşıyıcı sistemler arasından mezoporlu silika nanoparçacıklar (MSN) biyouyumluluk, düşük toksitite gibi özellikleri sayesinde sağlık alanında çeşitli uygulamalarda kullanılmaktadır. Mezopor silika nanoparçacıkların gözenekli yapıları ilacın sisteme yüklenmesini ve hedef bölgeye kontrollü bir şekilde verilmesini kolaylaştırırlar. Bu çalışmada bir antikanser ilaç olan siklofosfamid (CPH) yüklü mezopor silika nanoparçacıklar sentezlenerek teknesyum-99m ile radyoişaretlenmesi ve bu yapının biyolojik davranışının in vitro olarak incelenmesi amaçlanmıştır. Sentezlenen nanoparçacıkların parçacık boyutu, morfolojisi, ilaç hapsetme kapasitesi gibi parametreler incelenerek en uygun sentez koşulları belirlenmiştir. Nanoparçacıkların karakterizasyonu Fourier Dönüşümlü Kızılötesi Spektroskopisi (FTIR), Dinamik Işık Saçılım (DLS), Taramalı elektron mikroskobu (SEM) ile yapılmıştır. DLS analizine göre sentezlenen MSN‟ ler 125 ± 3,4 nm hidrodinamik yarıçapa sahiptirler. SEM görüntülerine göre de MSN‟ lerin küresel morfolojik yapıda ve 55 ile 70 nm boyutları arasında oldukları gözlenmiştir. Radyoişaretli Siklofosfamid yüklü mezopor silika nanoparçacıkların (99mTc-MSN-CPH) kalite kontrol çalışmaları İnce Tabaka Radyokromatografisi (TLRC) yöntemi kullanılarak gerçekleştirilmiştir. MSN-CPH nanoparçacıklar % 99,82 ± 0,25 verimle teknesyum-99m ile başarılı bir şekilde radyoişaretlenmiştir. Kalite kontrol çalışmaları yapıldıktan sonra siklofosfamid yüklü mezopor silika nanoparçacıkların sitotoksisite ve tutulum çalışmaları in vitro olarak MCF-7 ve MDA-MB-231 meme kanser hücreleri kullanılarak gerçekleştirilmiştir. 99mTc-MSN-CPH parçacıklarının MCF7 ve MDA-MB-231 hücrelerinde benzer tutulum gösterdiği bulunmuştur. Bu tez çalışmasında sentezlenen nano yapının, gelecekte kanser teşhis ve tedavisinde kullanılabilecek 99mTc ile radyoişaretli yeni nesil nanoteranostik sistemlerin geliştirilmesine katkıda bulunacağı düşünülmektedir.
Recently, the possibilities of nanoparticles (NP) in the transportation of therapeutic and target-specific drugs have been increasingly received by scientists and the pharmaceutical industry. Among these carrier systems, mesoporous silica nanoparticles have remarkable properties. Silica nanoparticles are used in various applications in the field of health thanks to their properties such as biocompatibility and low toxicity. Thanks to their porous structure, mesopore silica nanoparticles (MSN) make it easier to load the drug into the system and deliver it to the target area in a controlled manner. In this study, it was aimed to synthesize cyclophosphamide (CPH) loaded mesoporous silica nanoparticles, radiolabeled with technetium-99m and analyze the biological behavior of this structure in vitro. Optimum conditions were determined by examining parameters such as particle size, morphology, drug entrapment capacity of synthesized nanoparticles. The characterization of nanoparticles was carried out by Fourier Transform Infrared Spectroscopy (FTIR), Dynamic Light Scattering (DLS), Scanning electron microscopy (SEM). The synthesized MSNs have a hydrodynamic radius of 125 ± 3.4 nm according to DLS analysis. SEM images showed that nanoparticles have a spherical morphological structure and distributed between 55 and 70 nm in size. Quality control studies of radiolabeled Cyclophosphamide loaded mesopore silica nanoparticles (99mTc-MSN-CPH) were carried out using Thin Layer Radiochromatography (TLRC) method. MSN-CPH nanoparticles were successfully radiolabeled with technetium-99m in 99.82 ± 0.25% efficiency. After quality control studies, cytotoxicity and uptake studies of cyclophosphamide-loaded mesopore silica nanoparticles were performed in vitro using MCF-7 and MDA-MB-231 breast cancer cells. It was found that 99mTc-MSN-CPH particles showed similar uptake in MCF7 and MDA-MB-231 cells. It is thought that the nanostructure synthesized in this thesis will contribute to the development of new generation radiolabeled nanoteranostic systems with 99mTc that can be used in the diagnosis and treatment of cancer in the future.
Recently, the possibilities of nanoparticles (NP) in the transportation of therapeutic and target-specific drugs have been increasingly received by scientists and the pharmaceutical industry. Among these carrier systems, mesoporous silica nanoparticles have remarkable properties. Silica nanoparticles are used in various applications in the field of health thanks to their properties such as biocompatibility and low toxicity. Thanks to their porous structure, mesopore silica nanoparticles (MSN) make it easier to load the drug into the system and deliver it to the target area in a controlled manner. In this study, it was aimed to synthesize cyclophosphamide (CPH) loaded mesoporous silica nanoparticles, radiolabeled with technetium-99m and analyze the biological behavior of this structure in vitro. Optimum conditions were determined by examining parameters such as particle size, morphology, drug entrapment capacity of synthesized nanoparticles. The characterization of nanoparticles was carried out by Fourier Transform Infrared Spectroscopy (FTIR), Dynamic Light Scattering (DLS), Scanning electron microscopy (SEM). The synthesized MSNs have a hydrodynamic radius of 125 ± 3.4 nm according to DLS analysis. SEM images showed that nanoparticles have a spherical morphological structure and distributed between 55 and 70 nm in size. Quality control studies of radiolabeled Cyclophosphamide loaded mesopore silica nanoparticles (99mTc-MSN-CPH) were carried out using Thin Layer Radiochromatography (TLRC) method. MSN-CPH nanoparticles were successfully radiolabeled with technetium-99m in 99.82 ± 0.25% efficiency. After quality control studies, cytotoxicity and uptake studies of cyclophosphamide-loaded mesopore silica nanoparticles were performed in vitro using MCF-7 and MDA-MB-231 breast cancer cells. It was found that 99mTc-MSN-CPH particles showed similar uptake in MCF7 and MDA-MB-231 cells. It is thought that the nanostructure synthesized in this thesis will contribute to the development of new generation radiolabeled nanoteranostic systems with 99mTc that can be used in the diagnosis and treatment of cancer in the future.
Açıklama
Anahtar Kelimeler
Mezopor Silika Nanoparçacıklar, İlaç Taşıyıcı Sistemler, Siklofosfamid, Teknesyum-99m, İn Vitro, Mesoporous Silica Nanoparticles, Drug Delivery Systems, Cyclophosphamide, Technetium-99m, In Vitro
