乘載順鉑抗癌藥物的兩性梳狀共聚物微胞做為藥物傳遞之載體

Cisplatin-loaded amphiphilic graft copolymer micelles for drug delivery systems

巫佩玲(Pei-Ling Wu)

指導教授 ： 王麗芳

高雄醫學大學/生命科學院/醫藥暨應用化學研究所/碩士(2013年)

摘要

我們利用原子轉移自由基聚合法(Atom transfer radical polymerization, ATRP)合成一新穎的梳狀兩性共聚物 poly(ethylene glycol)-b-poly(ε-caprolactone)-g-poly(methacrylic acid) (MPCL-g-pMAA)。控制MPCL及pMAA的莫耳比例，我們製備出三種不同親/疏水比例的兩性梳狀共聚物 MPCL-g-pMAA；此共聚物在水中可自組裝形成微胞，內層為疏水端(PCL)，作為核心，外層為親水端(PEG、MAA)，作為穩定血流循環的外殼。利用MAA上的羧基(Carboxylic groups) 與抗癌藥物Cisplatin進行化學鍵結，達到承載藥物的功能。
我們利用動態光散射分析儀(Dynamic light scattering, DLS)以及穿透式電子顯微鏡(Transmission electron microscope, TEM)分析其粒徑大小及微胞型態。而隨著微胞表面親水嵌段上羧基(Carboxylic groups)量的上升，藥物的乘載量也相對提高，其粒徑大小也隨之變大。在藥物釋放部分，相同pH值下，最低親水嵌段的微胞藥物載體的釋放速率較其他兩者快。而其在細胞毒性測試上也具有較好的細胞毒殺效果。同時利用共軛焦顯微鏡（Confocal laser scanning microscopy, CLSM）觀測微胞載體經細胞胞噬(Endocytosis)之表現。

關鍵字

藥物載體 ； 微胞 ； 原子轉移自由基聚合法

並列摘要

In this study, we designed a novel comb-shaped amphiphilic copolymer, poly(ethylene glycol)-b-poly(ε-caprolactone)-g-poly (methacrylic acid) (MPCL-g-pMAA), which was synthesized by atom transfer radical polymerization (ATRP). We controlled the molar ratio of pMAA and MPCL to form three copolymers with different hydrophilic/hydrophobic characteristics. The MPCL-g-pMAA could self-assemble into micelles in aqueous solution with hydrophobic PCL in the center and hydrophilic PEG and MAA on the surface to increase circulation time in the blood. The carboxylic groups of pMAA were used to coordinate with an anticancer agent, Cisplatin, and the formed polymer-metal complexes could be used for cancer therapy.
We used dynamic light scattering (DLS) and transmission electron microscope (TEM) to observe sizes and morphologies of micelles with and without Cisplatin. The drug loading efficiency and the hydrodynamic diameter increased with increasing amount of the carboxylic groups of MPCL-g-pMAA. The MPCL-g-pMAA with the least hydrophilic block length of pMAA showed the highest drug release amount as well as the highest cytotoxicity. The cellular internalization was visualized using a confocal laser scanning microscopy (CLSM).

並列關鍵字

drug carrier ； micelle ； Atom transfer radical polymerization

參考文獻

1. http://www.ecancer.org.tw/AidantWay.aspx

2. Kerr, J. F.; Winterford, C. M.; Harmon, B. V., Apoptosis. Its significance in cancer and cancer therapy. Cancer 1994, 73 (8), 2013-26.

3. Uhrich, K. E.; Cannizzaro, S. M.; Langer, R. S.; Shakesheff, K. M., Polymeric systems for controlled drug release. Chemical reviews 1999, 99 (11), 3181-98.

4. Bennewitz, M. F.; Saltzman, W. M., Nanotechnology for delivery of drugs to the brain for epilepsy. Neurotherapeutics 2009, 6 (2), 323-36.

5. Torchilin, V. P., Targeted pharmaceutical nanocarriers for cancer therapy and imaging. The AAPS journal 2007, 9 (2), E128-47.