聚氰基丙烯酸乙酯藥物載體系統製備之研究

Studies on the Synthesis of Poly(ethyl cyanoacrylate) Nanoparticles as Drug Carrier Systems

李怡潔(Yi-Chieh Lee)

指導教授 ： 王勝仕

國立臺灣大學/工學院/化學工程學研究所/碩士(2014年)

https://doi.org/10.6342/NTU.2014.02823

摘要

在台灣已逐漸步入高齡化的社會，台灣失智症協會(Taiwan Alzheimer’s Disease Association)已估計台灣的失智人口到2060年時將逼近80萬人，而失智症中阿茲海默症之病患又佔其多數，如何有效地預防及治療阿茲海默症將會是一個相當重要之課題。

Clioquinol (CQ)為一種金屬螯合劑，已經在文獻中證實可以用以治療阿茲海默症(AD)，但由於CQ本身之特性導致其無法順利地通過血腦屏障(Blood brain barrier)；研究人員發現若使用奈米顆粒作為藥物載體，可利用其藥物載體之標靶性，可以使藥物通過血腦屏障並發揮其功效。

因已有許多文獻指出聚氰基丙烯酸烷基酯(Poly alkyl cyanoacrylate，PACA)及聚氰基丙烯酸丁酯(Poly butyl cyanoacrylate， PBCA)等具有具有生物相容性(Biocompatibility)及生物可降解性(Biodegradability)，可以作為藥物載體幫助藥物順利地送達目的地。此論文中主要是利用聚氰基丙烯酸乙酯(Poly ethyl cyanoacrylate，PECA)作為藥物載體，利用調整其起始條件，得到吾人所需之大小以通過血腦屏障，並測量其性質、藥物釋放速率等，以了解其特性，以便日後實際運用於治療阿茲海默症上。

關鍵字

阿茲海默症 ； 血腦屏障 ； Clioquinol ； 聚氰基丙烯酸乙酯

並列摘要

In Taiwan, we are entering aging society. Taiwan Alzheimer’s Disease Association estimates that the population of dementia in Taiwan will be near to 800000 in 2060. Alzheimer’s disease makes up the greatest number of cases among all causes of dementia. Therefore, how to prevent and cure Alzheimer’s disease effectively is becoming an important issue.

Clioquinol is one of the metal chelating agent and has been found to be beneficial in the treatment for Alzheimer's disease. While clioquinol itself cannot easily pass through the blood brain barrier, the research showed that, with nanoparticles used as the drug carriers, the targeting property/feature of the drug carriers would aid in the passage of clioquinol across the blood brain barrier and thus exerting its effects.

Many studies have demonstrated that, due to their biocompatibility and biodegradability, poly alkyl cyanoacrylates (PACA), and poly butyl cyanoacrylate (PBCA) can be used as the drug carriers and help the drugs reach the destination. In this thesis, the poly ethyl cyanoacrylate (PECA) was used as a drug carrier system. In order to obtain the proper size of PECA nanoparticle drug carrier to pass the blood brain barrier, several key parameters of the synthesis of PECA nanoparticle drug carriers were examined. The important properties/features along with the drug release rates of the PECA nanoparticle drug carrier were also determined. We believe the outcome from this research may contribute to the treatment for Alzheimer’s disease.

並列關鍵字

Alzheimer’s disease ； blood brain barrier ； Clioquinol ； poly ethyl cyanoacrylate

參考文獻

1. Wood, W.G., et al., Amyloid beta-protein interactions with membranes and cholesterol: causes or casualties of Alzheimer's disease. Biochimica Et Biophysica Acta-Biomembranes, 2003. 1610(2): p. 281-290.

3. Selkoe, D.J., Alzheimer's disease: Genes, proteins, and therapy. Physiological Reviews, 2001. 81(2): p. 741-766.

4. Liu, G., et al., Nanoparticle and other metal chelation therapeutics in Alzheimer disease. Biochim Biophys Acta, 2005. 1741(3): p. 246-52.

5. Cui, Z.R., et al., Novel D-penicillamine carrying nanoparticles for metal chelation therapy in Alzheimer's and other CNS diseases. European Journal of Pharmaceutics and Biopharmaceutics, 2005. 59(2): p. 263-272.

6. Lu, J.X. and G.F. Combs, Penicillamine - Pharmacokinetics and Differential-Effects on Zinc and Copper Status in Chicks. Journal of Nutrition, 1992. 122(2): p. 355-362.