Siklodekstrin Bağlı Poli(Laktid-Ko-Glikolid) Mikropartiküllerinin Sentezi, Karakterizasyonu, In vitro Kolesterol Gideriminde Kullanılabilirliği
Abstract
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 5o C’den 35o C’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.
References
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- Fournier R.L. Solute transport in biological systems. In Basic Transport Phenomena in Biomedical Engineering 1999; pp. 27-28, Taylor & Francis: Philadelphia, PA.
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Synthesis, Characterization and In vitro Cholesterol Removal Performance of Cyclodextrin Immobilized Poly (Lactide-Co-Glycolide)
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.
References
- Bjorkegren J., Packard C.J., Hamsten A. Accumulation of large very low density lipoprotein in plasma during intravenous infusion of a chylomicron-like triglyceride emulsion reflects competition for a common lipolytic pathway. J Lipid Res 1996; 37:76–
- Casper P., Glöckner P., Ritter H. Cyclodextrins in polymer synthesis: ınfluence of acrylate side groups on the ınitial rate of radical polymerization of various acrylate/methylated βcyclodextrin complexes in water. Macromolecules 2000; 33:4361-64.
- Yazar M., Yur F. Hiperkolesterolemik insanlarda plazma lipoprotein ve fosfolipid seviyeleri. YYU Vet Fak Derg 2003; 14:83-85.
- Gencosmanoğlu B., Alhan C., Bardak A., Turfan M., Yılmaz H., Hancı M. Evaluation of serum lipid levels as a risk factor for coronary artery disease in patients with spinal cord injury. Turk. Fiz. Tip Rehab. Derg. 2000; 3(2):57-63.
- Zhu K.J., Jiang H.L., Du X.Y., Wang J., Xu W.X., Liu SF. Preparation and characterization of hCG-loaded polylactide or poly(lactide-co-glycolide) microspheres using a modified water in- oil-in-water (w/o/w) emulsion solvent evaporation technique. J Microencapsul 2001; 18:247–260.
- Danhier F., Ansorena E., Silva J.M., Coco R., Le Breton A., Preat V. PLGA-based nanoparticles: an overview of biomedical applications. J Control Rel. 2012; 161(2):505-22. Shibusawa Y., Negishi I., Tabata Y., Ishikawa O. Mouse model of dermal fibrosis induced by one-time injection of bleomycin-poly(L-lactic acid) microspheres. Rheumatology 2008; 1:4Nie H., Lee L.Y., Tong H., Wang C. PLGA/chitosan composites from a combination of spray drying and supercritical fluid foaming techniques: New carriers for DNA delivery. J. Control Rel. 2008; 129: 207–214.
- Niesman M.R. The use of liposomes as drug carriers in ophthalmology. Drug Carr Syst 1992; 9:1-38.
- Eliaz R.E., Kost J. Characterization of a polymeric PLGA-injectable implant delivery system for the controlled release of proteins. J Biomed Mater Res 2000; 50:388–396.
- Tong Y., Wang S., Xu J., Chua B., He C. Synthesis of O,O-dipalmitoyl chitosan and its amphiphilic properties and capability of cholesterol absorption. Carbohydr Polym 2005; 60: 229–233.
- Tahir M.N., Lee Y. Immobilisation of β-cyclodextrin on glass: Characterisation and application for cholesterol reduction from milk. Food Chem 2013; 139:1-4
- Bereli N., Şener G., Yavuz H., Denizli A. Oriented immobilized anti-LDL antibody carrying poly(hydroxyethyl methacrylate) cryogel fo r cholesterol removal from human plasma. Mater Sci Eng 2011; 31:1078-1083
- Sieber R., Rehberger B.S., Walther B. Removal of cholesterol from dairy products. Encyclopedia of Dairy Sciences 2011; 2:734-740.
- Carol McClure D., Schiller N.L. Effects of Pseudomonas aeruginosa rhamnolipids on human monocyte-derived macrophages. Curr Microbiol 1996, 33:109-117.
- Tasdelen B., Kayaman N., Guven O., Baysal B.M. Investigation of drug release from thermo- and pH- sensitive poly(N-isopropylacrylamide/itaconic acid) copolymeric hydrogels. Poly Adv Technol 2004; 528:532-534.
- Nagaoka S., Mori Y., Tanzawa H., Kikuchi Y., Inagaki F., Yokota Y., Noishiki Y. Hydrated dynamic surfaces. ASAIO Journal 1987; 10:76-78.
- Fournier R.L. Solute transport in biological systems. In Basic Transport Phenomena in Biomedical Engineering 1999; pp. 27-28, Taylor & Francis: Philadelphia, PA.
- Dee K.C., Puleo D.A., Bizios R. Protein– surface interactions. In Tissue-Biomaterials Interactions 2002; pp. 45-49, John Wiley & Sons Inc.: Hoboken, NJ.
- Latour R.A., Biomaterials: Protein–surface Interactions. in: Wnek G, Bowlin G, editors. The Encyclopedia of Biomaterials and Bioengineering 2005; pp. 25-31, Taylor & Francis; New York.
- Vroman L., Adams A.L. Findings with the recording ellipsometer suggesting rapid exchange of specific plasma proteins at liquid solid interfaces. Surf Sci 1969; 16:438–446. Kılıç K., Kesim B., Sümer Z., Polat Z., Öztürk A, Tam seramik materyallerinin biyouyumluluğunun MTT testi ile incelenmesi. Sağlık Bilimleri Dergisi 2010;192:125-32. Mondalek F.G., Ponnurangam S., Govind J., Houchen C., Anant S., Pantazis P., Ramanujam R. Inhibition of angiogenesis- and inflammation-inducing factors in human colon cancer cells in vitro and in ovo by free and nanoparticle-encapsulated redox dye. J Nanobiotechnol 2010; 8:17.
Details
| Primary Language | Turkish |
|---|---|
| Subjects | Engineering |
| Journal Section | Editorial |
| Authors | |
| Publication Date | November 25, 2014 |
| Published in Issue | Year 2014 Volume: 35 Issue: 3 |