Melanoma tedavisine yönelik ikili ilaç içeren nanoyapılı lipid taşıyıcıların hazırlanması ve karakterizasyonu
Küçük Resim Yok
Tarih
2023
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Deri kanseri dünya çapında en yaygın görülen kanserlerden biridir. Melanoma tüm cilt kanseri vakalarının yaklaşık %4'ünü oluşturmakla birlikte cilt kanseri kaynaklı ölümlerinin büyük çoğunluğu (%75) oluşturur ve dünya çapında melanoma vakaları her geçen gün artmaktadır. İkili ilaç içeren nanoyapılı lipid taşıyıcıların melanoma hücrelerince seçimli ve yüksek oranda alınabilmesi için hücrelerde aşırı miktarda artan LAT-1 taşıyıcı proteininin ekspresyonu hedef alınmıştır. Bu hedefleme ile melanomanın tedavi edilebilmesi için tez kapsamında kemoterapötik ajanlar olarak doksorubisin ve trabektedin içeren ikili ilaç taşıyıcı sistemlerin geliştirilmesi hedeflenmiştir. İkili ilaç içeren LAT-1 hedefli NLC'ler sentezlenmiştir. Hazırlanan nanopartiküllerin karakterizasyon çalışmaları sonucunda, DSPE-PEG-Tirozin konjugatının başarı ile sentezlendiği ve ikili ilaç içeren LAT-1 hedefli NLC'lerin hidrodinamik boyutu 123,77 nm, PDI değeri 0,472 ve zeta potansiyel değeri -27,89 mV olarak bulunmuştur. Bu değerler melanoma tedavisinde başarılı bir hedefleme sunan ikili ilaç içeren nanopartiküllerin sentezinin gerçekleştirildiğini göstermektedir. İn vitro salım çalışmalarında ikili ilaç içeren hedefli NLC'lerin tümör mikroçevresi özelliği gösteren asidik koşullarda (pH 5) salım değerleri fizyolojik pH olan 7,4'e göre belirgin bir fark ile daha yüksek salım profili göstermektedir. Salım profili ayrıca kontrollü ve uzun süreli olarak gözlenmiştir.
Skin cancer is one of the most common cancers worldwide. Melanoma accounts for approximately 4% of all skin cancer cases, but accounts for the vast majority (75%) of skin cancer deaths and melanoma cases are increasing worldwide. In order to selectively and highly uptake the dual drug-containing nanostructured lipid carriers by melanoma cells, we targeted LAT-1 expression, which is increased excessively in cells. With this targeting, it is aimed to develop dual drug carrier systems containing doxorubicin and trabektedine as chemotherapeutic agents in order to treat melanoma. LAT-1 targeted NLCs containing dual drugs were synthesized. As a result of the characterization studies of the prepared nanoparticles, it was found that DSPE-PEG-Tyrosine conjugate was successfully synthesized and the hydrodynamic size of LAT-1 targeted NLCs containing dual drugs was 123.77 nm, PDI value was 0.472 and zeta potential value was -27.89 mV. These values indicate the synthesis of dual drug-containing nanoparticles that offer successful targeting in melanoma treatment. In in vitro release studies, the release values of targeted NLCs containing dual drugs in acidic conditions (pH 5), which are characteristic of tumor microenvironment, show a higher release profile with a significant difference compared to the physiological pH of 7.4. The release profile was also observed in a controlled and long-term release profile.
Skin cancer is one of the most common cancers worldwide. Melanoma accounts for approximately 4% of all skin cancer cases, but accounts for the vast majority (75%) of skin cancer deaths and melanoma cases are increasing worldwide. In order to selectively and highly uptake the dual drug-containing nanostructured lipid carriers by melanoma cells, we targeted LAT-1 expression, which is increased excessively in cells. With this targeting, it is aimed to develop dual drug carrier systems containing doxorubicin and trabektedine as chemotherapeutic agents in order to treat melanoma. LAT-1 targeted NLCs containing dual drugs were synthesized. As a result of the characterization studies of the prepared nanoparticles, it was found that DSPE-PEG-Tyrosine conjugate was successfully synthesized and the hydrodynamic size of LAT-1 targeted NLCs containing dual drugs was 123.77 nm, PDI value was 0.472 and zeta potential value was -27.89 mV. These values indicate the synthesis of dual drug-containing nanoparticles that offer successful targeting in melanoma treatment. In in vitro release studies, the release values of targeted NLCs containing dual drugs in acidic conditions (pH 5), which are characteristic of tumor microenvironment, show a higher release profile with a significant difference compared to the physiological pH of 7.4. The release profile was also observed in a controlled and long-term release profile.
Açıklama
Anahtar Kelimeler
Biyokimya, Biochemistry
