磁性幾丁聚醣奈米粒子包覆喜樹鹼之研究

Magnetic chitosan nanoparticles for camptothecin delivery

李新和(Hsin-Ho Li)

指導教授 ： 林忻怡

國立臺北科技大學/工程學院/化學工程研究所/碩士(2013年)

摘要

此研究應用智慧型載體的設計概念與癌症化學治療作結合，使藥物載體具有磁導功能，並以天然高分子幾丁聚醣 (Chitosan， Cs) 包覆在外，使化療藥物喜樹鹼(Camptothecin， CPT)延緩藥物釋放，並且在患部給予外加磁場，提高患部藥物濃度，降低其他器官的藥物濃度，減少化療可能發生之副作用。
合成原理先以檸檬酸鈉(Sodium citrate)當作界面活性劑修飾奈米磁珠(Iron oxide nanoparticles，Fe3O4)表面時，因為官能基的解離而使粒子帶有表面負電荷。利用相異電荷相吸原理，使帶有正電荷幾丁聚醣包覆奈米磁珠(CS/Fe3O4)。之後再利用喜樹鹼因PH值由鹼變中性，此時水溶性的喜樹鹼carboxylate會轉換成非水溶性的lactone，吸附在幾丁聚醣包覆奈米磁珠裡(CPT/CS/Fe3O4)。
實驗結果得知藥物載體粒徑約 300nm，在藥物負載率方面能達到 41% 左右。體外藥物釋放數據也顯示，在有外加磁場下，的確能有效加速藥物的釋放。細胞毒性測試結果也證實，CS/Fe3O4對細胞並沒有毒殺效果，而CPT/CS/Fe3O4與CS/Fe3O4相較下，明顯提高了對癌細胞的毒殺效果。多項結果都能表示智慧型藥物載體在未來化療領域更有應用與研究價值。

關鍵字

奈米磁珠 ； 檸檬酸鈉 ； 幾丁聚醣 ； 喜樹鹼

並列摘要

he purposes of this study for the multifunctional nanoparticles -mediated cancer chemotherapy drug delivery, their multifunction includes the following steps. Firstly, the drug carrier can be controlled by superparamagnetism. Secondly, the chemotherapy drug (Camptothecin， CPT) was adsorbed in the natural polymeric carrier to form nanoparticles with low toxicity. We developed the new purpose of the multifunctional
chitosan (Cs) nanoparticles-mediated CPT release for cancer therapy.
Surface modification of Fe3O4 nanoparticles was carried out by treating the nanoparticles with sodium citrate. Because dissociation of functional groups with particles leaving the negative surface charge. Using dissimilarity charges attract principles, then positive charge of chitosan coated Fe3O4 nanoparticles (CS/ Fe3O4). Water-soluble CPT carboxylate converted into its water-insoluble lactone form due to the acidification with decreasing pH. The lactone-formed CPT was immediately precipitated and adsorbed to the chitosan coated Fe3O4 nanoparticles.
According to the results, the CPT/CS/Fe3O4 was nanoscale of particle size (around 300 nm) but with low drug loading efficiency (above 41%). In vitro drug release data show that it can effectively accelerate the drug release under an external magnetic field. Cytotoxicity test results also confirmed, the CS/ Fe3O4 is low toxic effect on cancer cells, but the CPT/CS/ Fe3O4 is higher toxic effect on cancer cells. The CPT/CS/ Fe3O4 constitutes a useful approach for the future design of drug carriers.

並列關鍵字

Iron oxide nanoparticles ； Sodium citrate ； Chitosan ； Camptothecin

參考文獻

39. 詹宗桂、 鍾宜璋，「磁場誘導藥物控制釋放之載體設計」，化學，第六十八卷，第三期，2010，第1-11頁。

1. A. Huczko, Template-based synthesis of nanomaterials. Appl. Phys. A, 2000. 70: p. 365-376.

2. C. Sun, J.S. Lee, and M. Zhang, Magnetic nanoparticles in MR imaging and drug delivery. Adv Drug Deliv Rev, 2008. 60(11): p. 1252-65.

5. K. Donadel, et al., Synthesis and characterization of the iron oxide magnetic particles coated with chitosan biopolymer. Materials Science and Engineering: C, 2008. 28(4): p. 509-514.

8. W. Li, et al., First-pass contrast-enhanced magnetic resonance angiography in humans using ferumoxytol, a novel ultrasmall superparamagnetic iron oxide (USPIO)-based blood pool agent. J Magn Reson Imaging, 2005. 21(1): p. 46-52.