Siklodekstrin Bağlı Poli(Laktid-Ko-Glikolid) Mikropartiküllerinin Sentezi, Karakterizasyonu, In Vitro Kolesterol Gideriminde Kullanılabilirliği

Emine Yalçın, Figen Çiçek, Kültiğin Çavuşoğlu
2.473 900

Abstract


Özet. Bu çalışmada siklodekstrin tutuklanmış poli (laktid-ko-glikolid) (PLGA) mikropartiküllerinin sentezi, karakterizasyonu ve in vitro kolesterol gideriminde kullanılması hedeflenmiştir. Biyobozunur özellikte PLGA mikropartiküllerinin canlı sistemlerde kullanılabilirliği oldukça yüksektir. Bu tür malzemelerin uygulama sonrası vücuttan alınması için cerrahi işleme ihtiyaç duyulmaması önemli bir avantajdır. Bu çalışmada PLGA partikülleri kopolimerizasyon yöntemi ile sentezlenmiş ve in vitro kolesterol gideriminde model biyomalzeme olarak seçilmiştir. Partikül sentezi, polilaktik asit (PLA) ve poliglikolik asit (PGA) mol oranı 75/25, 50/50, 25/75 olacak şekilde 3 farklı monomer karışımı kullanılarak gerçekleştirilmiştir. Siklodekstrin tutuklanarak partiküllerin kolesterole karşı afinitesi arttırılmıştır. Siklodekstrin tutuklanmış PLGA mikropartiküllerinin biyouyumluluk özellikleri hemoliz, kan proteinleri adezyonu, temas açısı ölçümleri ve kararlılık ile incelenmiştir. Karakterizasyon çalışmaları sonrasında mikropartiküller in vitro kolesterol uzaklaştırılmasında kullanılmıştır. Partikül bileşimi, ortam pH’sı ve sıcaklık parametrelerinin giderim performansı üzerine etkisi test edilmiştir. Tüm mikropartiküller yüksek biyouyumluluk özelliği sergilemiştir. PGA oranının artması ile birlikte hemolitik aktivite ve protein adezyonunun azaldığı belirlenmiştir.  Ayrıca partiküldeki poli laktik asit faz oranının azalmasıyla su ile temas açılarının da azaldığı belirlenmiştir. Ortam pH’sının ve sıcaklığının kolesterol giderimini önemli derecede etkilediği belirlenmiştir. En yüksek kolesterol giderimine pH 7.0 değerinde PLA/PGA: 25/75  mikropartikül bileşimi ile ulaşılmıştır. Ortam sıcaklığının 5oC’den 35oC’ye arttırılması ile kolesterol gideriminin 1.36 kat arttığı gözlenmiştir. PLGA partiküllerinin kolesterol gideriminde etkili bir biyouyumlu materyal olduğu, siklodekstrin immobilizasyonunun kolesterol giderim performansını arttırdığı belirlenmiştir.

 

Abstract. In this study, the synthesis, characterization and in vitro cholesterol removal performance of cyclodextrin immobilized poly (lactide-co-glycolide) (PLGA) was aimed. The biodegredable poly PLGA microspheres are widely used in humans. After treatment process, the removal of these materials from the body without an operational process is an important advantage.  In this study, PLGA particles were synthesized by copolymerization method and used in cholesterol removal as a model biomaterial. Particle synthesis was performed with using different monomer mixtures as polylactic acid (PLA)/ polyglycolic acid (PGA) mol ratios of 75/25, 50/50, 25/75. The affinity of PLGA particles for cholesterol was increased with cyclodextrin immobilization. The biocompatibility of cyclodextrin immobilized PLGA particles were investigated by using hemolysis, blood protein adhesion, contact angle measuremet and stability. Particles were used in cholestrol removal after characterization studies. The effects of particle composition, medium pH and temperature on removal performance were tested. High biocompatibility was observed in all compositions. Protein adhesion and hemolytic activity was decreased with increasing PGA ratio. And also contact angles with water were decreased with decreasing poly lactic acid phase ratio in compositions. Medium pH and temperature was affected importantly cholesterol removal. Maximum cholesterol removal was obtained with PLA/PGA:25/75 composition at pH 7.0. Cholesterol removal was increased 1.36 times with increasing medium temperature 5oC to 35oC. PLGA particles were an effective biocompatible material for cholesterol removal and cyclodextrin immobilization increased the cholesterol removal performance.


Keywords


Biocompatibility, cyclodextrine, cholesterol, poly (lactide-co-glycolide)

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