Gen tașınması için olası bir yaklașım; Poli 2-oksazolin tabanlı vektörler

Yıl 2014, Sayı: 2, 113 - 132, 01.06.2014

Aslı Kara İmran Vural Özgür Yılmaz Asuman Bozkır

Öz

Günümüzde, sentetik polimerlerin ilaç ve gen taşıyıcı sistem olarak kullanımı artan bir hızla devam etmektedir. Bunlar arasında, yüksek biyouyumluluk, görünmezlik stealth etkisi, düşük ortalama molekül dağılımı, yüksek terapötik yanıt, ilaç ve gen taşıma için polimer uç gruplarına eklenen fonksiyonel gruplar ile yüksek fonksiyonellik ve kimyasal yapının kolay değiştirilebilmesi ile farklı moleküllerin taşınması gibi çok yönlülük özellikleri ile 2-oksazolinler gen taşıyıcı sistemler olarak umut verici materyallerdir ve bu kapsamda yeni bir polimerik platform oluşturmaktadırlar. Özellikle polimerik terapötik olarak POx, PEG ile eşit düzeyde protein etkileşimi göstermesine rağmen, düşük spesifik olmayan organ birikimi göstermektedir. Bununla birlikte kimyasal stabilitesi de PEG’e göre önemli ölçüde daha iyidir. Günümüzde kullanılan PEG’lenmiş etkin maddelerin sürekli uygulanma zorlukları, immünolojik yanıt oluşturma, hızlandırılmış kan klerensi, biyoparçalanır olmayışı ve vücutta birikimi gibi dezavantajlarından dolayı, PEG yerine hidrofilik POx kullanımı iyi bir tercihtir. Son zamanlarda, etkin madde taşıyıcı özelliklerinin yanı sıra, gen tedavi uygulamalarında da POx polimerleri potansiyel bir alternatif olarak tartışılmaktadır. Gen taşınmasında POx’un kısmi hidrolizi ile sentezlenen PEI’nin in vitro hücre kültüründe düşük sitotoksisite ve yüksek gen aktarım etkinliği sergilemesi ve DNA ile sıkı kompleks oluşturma ve polimer kondensasyon kapasitesinin gen aktarımı için uygun olması gibi avantajları nedeniyle günümüzde araştırmacılar tarafından sıklıkla tercih edilmektedir. Bu derlemede işlevsel özellikleri ile Poli 2-oksazolin ler ele alınmış ve gen taşımadaki başarılı uygulamalarına örnekler verilerek vektör olarak kullanımlarının avantajları ile ilgili bilgilere yer verilmiştir.

Anahtar Kelimeler

Sentetik polimer, Poli 2-oksazolin, Gen tedavisi

A possible approach for gene transfer; Poly 2-oxazoline based vectors

Öz

Nowadays, the use of synthetic polymers in drug and gene delivery applications continues at an accelerated rate. Among these, as gene delivery system 2-oxazolines are promising materials with high biocompatibility, stealth effect, lower average molecular weight distribution, higher therapeutic response, higher functionalization with functional groups attached to the polymer end groups to drug and gene delivery and versatility features to deliver the different molecules by changing easily the chemical structures and they form a new polymeric platform. Especially as polymeric therapeutically POx, although equally well protein interaction with PEG and shows low non-specific organ accumulation. However, the chemical stability is significantly better than PEG. In addition, the use of POx instead of hydrophilic PEG is a good option due to disadvantages as consistent application of currently used PEGylated drugs, immunological response, accelerated blood clearance, non-biodegradability and accumulation in the body. Recently, besides active substance delivery properties, POx is also discussed as a potential alternative in gene therapy applications. Recently, PEI synthesized by partial hydrolysis of POx frequently choosen by researches for gene delivery applications because of its advantages, such as low cytotoxicity in cell culture and higher gene transfection efficiency and also forming tight complex with DNA and compatibility for condensation capacity to gene transfection. In this review, the functional properties of poly 2-oxazoline and their advantages about use as a vector with succesful applications of gene delivery were discussed.

Anahtar Kelimeler

Synthetic polymers, Poly 2-oxazoline, Gene therapy

Kaynakça

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