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Sustained Release of Chondroitiase and Growth Factors from Chitosan Nanoparticles for Repairing the Hemisection Spinal Cord Injured Primate
|Contributors: ||NTOU:Department of Food Science|
|Issue Date: ||2011-06-28T05:52:46Z
|Abstract: ||摘要:在組織工程上，生長因子和細胞為神經損傷修復中重要的影響因子，在醫療策略上給予外源性的生長因子，可保護損傷的神經組織並促進再生，來改善神經傳導的功能。目前已證實酸性纖維母細胞生長因子(acidic fibroblast growth factor；aFGF)直接注射或混合在生物膠中，運用於脊髓神經修復上具有顯著的效果。本研究是將幾丁聚醣(chitosan)與褐藻醣膠(fucoidan)或肝素(heparin)以聚電解質作用(polyelectrolyte)形成一奈米粒攜帶aFGF，進而達到控制釋放表現，修復受損的神經細胞。在幾丁聚醣-褐藻醣膠奈米粒特性部分，粒徑大小約為360~500nm，表面電位約為-23mV；另外幾丁聚醣-肝素奈米粒粒徑大小為240nm。在預實驗部分，首先以牛血清蛋白(bovine serum albumin, BSA)做為幾丁聚醣-褐藻醣膠奈米粒的攜帶對象，實驗結果顯示，在pH值為6時，幾丁聚醣-褐藻醣膠奈米粒對BSA之包覆率為35%；BSA在第一天有較大釋放量，六天的累積釋放率達50%。以幾丁聚醣-褐藻醣膠奈米粒攜帶aFGF做控制釋放實驗，第一天釋放濃度亦較大，約為28 ng/ml；但第二天後aFGF釋放濃度逐漸趨緩，直到第七天aFGF釋放濃度為37 ng/ml。以肝素-幾丁聚醣奈米粒攜帶aFGF做控制釋放實驗，結果顯示，經過20天aFGF仍有連續性釋放表現。比較肝素與褐藻醣膠兩種材料，推測硫酸基團的含量可能是關鍵因素。未來將改變硫酸基團在褐藻醣膠的含量，探討酸性纖維母細胞生長因子與褐藻醣膠的作用力，期待能設計出具高包覆率及長時間釋放的載體系統。此外，也將進行體外及動物實驗以模擬臨床前人類損傷治療的可行性。|
Abstract:In tissue engineering, growth factors and cells are important elements for repairing nerve injuries. Supplemented with exogenous growth factors is an effective medical strategy for protecting nerve injury and promoting nerve regeneration. It has been demonstrated that acidic fibroblast growth factors have great effect for repairing spinal cord injuries by injecting directly or mixing in fibrin glue. The aim of this study is to prepare new nanoparticle systems, chitosan/heparin and chitosan/fucoidan, based on polyelectrolyte complexation of negatively charged heparin or fucoidan with positively charged chitosan. These nanoparticles are prepared for controlled release of acidic fibroblast growth factors for spinal cord repair. According to our experimental results, particle sizes of chitosan/fucoidan and chitosan/heparin were 360~500 nm and 240nm respectively. The zeta potential of chitosan/fucoidan nanoparticles were -23mV. For preliminary experiments, BSA was used as a model drug for controlled release from chitosan/fucoidan nanoparticles. The results expressed that entrapment efficiency of BSA in chitosan/fucoidan nanoparticles was 35%. Burst release of BSA appeared for the first day. Accumulative release percentage arrived 50% for six days release. For control release of aFGF from chitosan/fucoidan nanoparticles, 28ng/ml of aFGF was release for the first day, and then, 37ng/ml of aFGF was released for seven days release. For chitosan/heparin nanoparticles, aFGF can be sustained release for 20 days. A comparison of heparin and fucoidan, the amount of sulfated groups might be a key factor for binding aFGF. Therefore, the percentage of sulfated groups of fucoidan will be changed in this project for studying the interaction between aFGF and fucoidan. We expect to design a carrier system with high entrapment efficiency and long term sustained release. Furthermore, in vitro and in vivo experiments will also be done as a preclinical trial before clinical application in the next year.
|Appears in Collections:||[食品科學系] 研究計畫|
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