Kanser hücrelerine hedefli biyomimetik ilaç taşıma sistemlerinin hazırlanması, karakterizasyonu ve biyopotansiyelinin araştırılması
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Dosyalar
Tarih
2016
Yazarlar
Dergi Başlığı
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Yayıncı
Ege Üniversitesi, Fen Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Epitelyal over kanseri kadınlarda jinekolojik kanserlerden en fazla ölüme neden olan türdür. Manyetik ajanlar tümörlü dokuya dışarıdan uygulanan manyetik alan yoluyla direk olarak yönlendirilerek ilaç preparatlarının yan etkilerinin azaltılmasına yardımcı olurlar. Antineoplastik bir ilaç olan doksorubisin klinikte meme, over gibi birçok kanserin tedavisinde kullanılmaktadır. Eritrosit vezikülleri kişinin kendi hücrelerinden hazırlanması dolayısıyla ilaç taşıyıcı sistem olarak biyouyumluluk sorunu ortadan kaldırabilmektedir. Çalışma kapsamında doksorubisin yüklü, nişasta ve PEG diasit kaplı manyetik nanopartiküller sentezlendi. Nanopartiküller, folat ligandı takılı eritrosit ghost hücrelerinden extruder ile oluşturulan veziküller içerisine yüklendi. Hazırlanan nanoboyutlu ilaç taşıyıcı biyomimetik sistemin in vitro ilaç salım çalışmalarının ardından biyouyumluluk testleri ve over kanseri hücreleri üzerinde sitotoksisite çalışmaları yapıldı. Elde edilen sonuçlara göre biyomimetik ilaç taşıma sisteminin kontrollü ilaç salımı yaptığı, biyouyumlu olduğu ve folat reseptörü ile etkileşerek hücrelerde sitotoksisite yarattığı bulundu. Dişi fareler üzerinde gerçekleştirilen biyodağılım çalışması ve ex vivo analizlerde ilaç taşıyıcısının folat reseptörü aracılığıyla ve manyetik olarak hedef dokuda birikebildiği saptandı. Sonuç olarak, biyomimetik tasarlı doksorubisin taşıma sisteminin over kanserinde kişiselleştirilmiş tedavi sağlama potansiyeli olduğu düşünülmektedir.
Epithelial ovarian cancer is the most leading of cause of death in women with gynecological cancer. Magnetic agents help to reduce the side effects of pharmaceutical preparations by externally applied magnetic field to tumor tissue. As an antineoplastic agent, doxorubicin is used for treatment of many cancers such as breast, ovarian etc. Erythrocyte vesicles prepared from the body's own cells can eliminate the problem of biocompatibility as a drug delivery system. In this study, doxorubicin loaded and starch and PEGdiacid coated magnetic nanoparticles were synthesized. Magnetic nanoparticles were encapsuled into vesicles that formed by the extruder device from erythrocyte ghost cells that was folate ligand anchored to. Followed by the in vitro drug release studies of nano sized biomimetic drug delivery system, biocompatibility tests and cytotoxicity studies on ovarian cancer cell lines were performed. Based on the data, it was found that biomimetic drug delivery system has a controlled drug release profile, biocompatible and causes cytotoxicity in cells by interacting with folate receptor. In the biodistribution studies carried out on female mice and ex vivo analysis, drug carriers were found to accumulate in the target tissues via folate receptor and magnetic field application. As a result, it is thought that the designed biomimetic doxorubicin transport systems have the potential to provide personalized treatment in ovarian cancer.
Epithelial ovarian cancer is the most leading of cause of death in women with gynecological cancer. Magnetic agents help to reduce the side effects of pharmaceutical preparations by externally applied magnetic field to tumor tissue. As an antineoplastic agent, doxorubicin is used for treatment of many cancers such as breast, ovarian etc. Erythrocyte vesicles prepared from the body's own cells can eliminate the problem of biocompatibility as a drug delivery system. In this study, doxorubicin loaded and starch and PEGdiacid coated magnetic nanoparticles were synthesized. Magnetic nanoparticles were encapsuled into vesicles that formed by the extruder device from erythrocyte ghost cells that was folate ligand anchored to. Followed by the in vitro drug release studies of nano sized biomimetic drug delivery system, biocompatibility tests and cytotoxicity studies on ovarian cancer cell lines were performed. Based on the data, it was found that biomimetic drug delivery system has a controlled drug release profile, biocompatible and causes cytotoxicity in cells by interacting with folate receptor. In the biodistribution studies carried out on female mice and ex vivo analysis, drug carriers were found to accumulate in the target tissues via folate receptor and magnetic field application. As a result, it is thought that the designed biomimetic doxorubicin transport systems have the potential to provide personalized treatment in ovarian cancer.
Açıklama
Anahtar Kelimeler
Doksorubisin, Folat Reseptör Hedefli İlaç, Manyetik İlaç Taşıma Sistemleri, Eritrosit Veziküller, Kişiselleştirilmiş Kanser Tedavisi, Doxorubicin, Folate Receptor Targeted Drug, Magnetic Drug Delivery System, Erythrocyte Vesicles, Personalized Cancer Therapy
