利用幾丁聚醣與玻尿酸形成的奈米粒子作為Docetaxel載體的製備與特性研究

Preparation and Characterization of Docetaxel-loaded Nanoparticles Composed of Chitosan/Hyaluronic Acid

林芝蕙(Chih-Hui Lin)

指導教授 ： 許明照

臺北醫學大學/藥學院/藥學研究所/碩士(2012年)

摘要

大部分的抗癌藥物為疏水性化合物，進入人體後因吸收不佳而易被體內的內皮網狀系統辨識而被快速清除，且因無法精準地到達腫瘤處，故需的提高使用劑量，但因此衍生許多副作用。本研究利用奈米載體系統來乘載藥物，因其粒子顆粒較小，可避免被內皮網狀系統辨識清除，因此能夠在腫瘤細胞中存留較久時間進而達到較好的治療效果並減低副作用。
本研究利用低分子量幾丁聚醣（Chitosan）和低分子量玻尿酸（Hyaluronic acid）形成一簡單的離子性複合體來開發一種新型的奈米粒子系統，透過兩者成分之相對比率不同以調控顆粒大小和界面電位。而後利用共聚法(Coacervation)將難溶性藥物多西紫杉醇(Docetaxel)包覆在奈米粒子中，以達到承載抗癌藥物並安全地增強抗癌藥物的遞送之目的。
由此本研究先取得幾丁聚醣與玻尿酸反應後得最適宜的奈米粒子大小組別，再利用其中三個組別，分別是幾丁聚醣與玻尿酸charge ratio比為7.13、3.58和0.45這三種所形成的奈米粒子來承載包覆多西紫杉醇。製成的多西紫杉醇高分子聚合物奈米粒子粒徑大小在110~840.9nm之間，界面電位在-36 ~ +8.32之間，而藥物包覆率最高能夠達到92.76%，在穿透式電子顯微鏡中也可觀察到所形成的奈米粒子確實是圓形的小顆粒。顯示出利用這種製成確實能夠將難溶性藥物包覆住並且形成奈米粒子，而未來我們還會繼續完成藥物釋放與後續的體外體內試驗，來完成抗癌藥物高分子聚合物奈米輸送載體的開發。

關鍵字

奈米粒子 ； 玻尿酸 ； 幾丁聚醣 ； 共聚法

並列摘要

Most anti-cancer drugs are hydrophobic compounds, so they are difficult to be uptaken and easy to be recognized and cleared rapidly by the reticuloendothelial system(RES). Besides, they are not specific to tumor site; therefore, dose is increased and which causes unexpected side effects. Nanoparticle drug delivery system provides a smaller size carrier for those anti-cancer drugs, protects and avoids them identified and cleared by RES. Nanoparticles are able to prolong the circulation in body and that prolong period time the tumor site.
In this study, a novel nanoparticle system was prepared using a simple and mild polyelectrolyte complexation method upon addition of low-molecular weight chitosan (CS) and hyaluronic acid (HA) solution, and their ratio controlled different particle size and the zeta potential value. Furthermore, docetaxel was ;oaded into the CS-HA nanoparticles by coacervation technology.
Three groups (charge ratio 7.13, 3.58 and 0.45) were selected to form docetaxel CS-HA nanoparticles. The range of the particle size is 110~840.9nm, and the range of zeta potential is -36~+8.32. The nanoparticles reached 92.76% encapsulation efficiency, and we can see the morphology from TEM. Our research shows that using coavervation could form docetaxel CS-HA nanoparticles, and in the future, the drug release test, in vitro and in vivo test will be go on to complete the development of polymeric nanoparticle delivery system in anti-cancer drug.

並列關鍵字

nanoparticles ； Hyaluronic acid ； chitosan

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