聚酸酐為用酸酐鍵結而成之高分子材料，具有生物可分解性和生物相容性的性質，且尤其具有表面降解的特性，當做藥物載體時有良好、易控制釋放的優點而廣受到醫藥學界的重視。
我們藉由熔融縮合的方法成功的合成出聚乙二醇-聚癸二酸酐二團聯共聚物。團聯共聚合物所使用材料的癸二酸和聚乙二醇都已經被FDA認可准許使用在人體內。聚癸二酸是一種疏水性的高分子，它跟聚乙二醇共聚合之後提供了一個很好的包覆疏水性藥物的環境以及在水相環境下有很好的藥物控制釋放機制。此外在藥物釋放系統裡面，聚乙二醇是一種被廣泛使用的親水性高分子，其主要的功能在於可以避免微胞粒子被巨噬細胞吞噬。在本文當中，我們將利用不同比例的聚乙二醇/聚癸二酸酐進料比，控制高分子的親疏水比例並探討此高分子之特性的差別。目前製備出三種不同親疏水比的共聚合物其分子量介於9500到14500之間，而且在聚癸二酸酐的進料比例較高的時候，其高分子的分子量也比較大。這樣的兩性高分子可藉由在水溶液中自我組裝的機制，形成具有奈米等級的高分子微胞顆粒，我們利用溶劑置換法去製備高分子微胞，其大小分佈在100到150nm之間，且疏水鏈段越長其所形成的微胞顆粒就會越大。在包覆疏水性抗癌藥物紫杉醇之後，微胞粒徑並沒有很大的差別。利用SEM觀察微胞的型態發現微胞是呈現球型的形狀。在材料降解的方面，由於聚酸酐對於水跟溫度的不穩定性，所以在37℃緩衝溶液下的降解是很快速的，在培養箱6個小時之後，不管哪一種比例的微胞皆有30~40%比例的材料被降解掉，之後的降解則會趨於緩慢，降解5天之後，約有70~80%的材料會被降解。
本研究是製備奈米微胞去包覆疏水性抗癌藥物--紫杉醇。紫杉醇亦稱為紅豆杉醇，乃從太平洋紫杉(Taxus brevifolia)的樹皮、葉片或是枝幹中萃取出來。在臨床測試中已經證實紫杉醇可以有效的治療一些惡性腫瘤，例如：轉移性乳癌、卵巢癌。
藥物包覆效率的結果，疏水鏈段較短的團聯聚合物所做成的微胞的包覆效率最好，包覆效率為41.51±0.71%。體外模擬藥物釋放速率結果，發現到一開始有很大的突然釋放(initial burst)的情形，會有這樣的情況可能是因為有很多的藥物其實只是卡在或是被包埋在較接近微胞表面孔洞的位置，所以很容易被釋放出來而造成一開始釋放很快。之後的釋放則較為緩慢，大約在5天之後會完全釋放完畢。綜合上面的結果，我們所製備的高分子微胞可以應用在短效的局部抗癌的治療上面。

A series of biodegradable poly (ester-anhydride), Poly(sebacic anhydride-co-ethylene glycol), was prepared by melt condensation for use in advanced drug delivery applications. Sebacic acid, a hydrophobic monomer, was copolymerized with PEG in order to produce water-insoluble polymers capable of providing continuous drug release kinetics following immersion in an aqueous environment. Poly ethylene glycol(PEG) can reduce particle clearance from bloodstream by macrophages and was a FDA approved polymer. In this paper, we changed various amounts of PEG (15~35% by mass) incorporated into the backbone of the polymers to allow tuning of particle surface properties.
The diblock copolymers were synthesized with the molecular weight range of 9,500~14,500 Da without any catalyst. Copolymers of higher molecular weights were obtained by increasing poly (sebacic anhydride) content.
The self-assembly of this water-insoluble diblock copolymer formed nanoparticles by solvent displacement method. The mean diameters of micelles were less than 200nm and exhibited low polydispersity index.
The degradation of polymeric micelles was studies by measuring the sebacic acid concentration in phosphate buffer. The result showed that a rapid degradation occurred during first 6 hr, followed by a slow degradation. After 5 days, about 70~80% of polymeric micelles core were degraded.
The drug encapsulation efficiency and the in vitro drug release kinetics were measured by high-performance liquid chromatography (HPLC). Of all, the entrapment efficiency of taxol-loaded micelles were 10.31~40.51%. The longer hydrophobic chain was, the lower its entrapment efficiency was. The drug release from mPEGPSA nanoparticle was found to be biphasic with an initial burst of 60~70% during the first 2hr, followed by a sustained release with 100% accumulative drug release after 5 days.

【1】Clemson Advisory Board for Biomaterials “Definition of the word biomaterial, Thc 6th Annnal Intermalionel Biomaterial Symposium, 1974, p20-24.
【2】Orloff L.A., Domb A.J., Teomim D., Fishbein I., Golomb G., Advanced Drug Delivery Reviews, 24, 1997, p3–9.
【3】Shikanov A., Kumar N., Abraham, Domb A.J., Israel Journal of Chemistry, 45, 2005, p393–399.
【4】Teomim D., Mader K., Bentolila A., Magora A, Domb, A. J. , Biomacromolecules , 2, 2001, p1015–1022.
【5】Shikanov A., Vaisman B., Krasko, M.Y., Nyska A., Domb A.J., Journal of Biomedical Materials Research Part A, 69A, 2004, p47–54.
【6】 Jay P. J., Sweta Modia, Domb A.J., Kumar N., Journal of Controlled Release, 103, 2005, p541–563.
【7】Hill J.W., J. Am. Chem. Soc., 52, 1930, p4110–4114.
【8】Rosen H.B., Chang J., Wnek G.E., Linhardt R.J., Langer R., Biomaterials,4, 1983, p131-133.
【9】Kumar N., Langer R., Domb A.J., Advanced Drug Delivery Review, 54, 2002, p889-910.
【10】 Katti D.S., Lakshmi S., Langer R., Laurencin C.T., Advanced Drug Delivery Reviews, 54, 2002, p933–961.
【11】Shieh L., Tamada J., Chen I., Pang J. ,Domb A.J., Langer R.,
J. Biomed. Mater. Res., 28, 1994, p1465–1475.
【12】Goepferich A., Langer R., J. Polym. Sci. Part A: Polym. Chem., 1993, 31, p2445-2458.
【13】Gopferich A., Biomaterials, 17, 1996, p103–114.
【14】 Gopferich A., Tessmar J., Advanced Drug Delivery Reviews, 54, 2002, p911–931.
【15】Alekha K.D., Greggrey C, Cudworth II, Journal of Pharmacological and Toxicological Methods, 40, 1998, p1–12.
【16】Ghosh S., Journal of chemical research, 2004, 2004, p241–246.
【17】 Gao X., Cui Y., Levenson R.M, Chung L.W K & Nie S., Nature biotechnology, 22, 2004, p969–976.
【18】Vicent M. J., Duncan R., TRENDS in Biotechnology, 24, 2006, p39–47.
【19】 Georg G.I., Chen T.T., Ojima I., Vyas D.M., Am. Chem. Soc., 1995.
【20】Tsavaris NB, Kosmas C, Cancer Chemother Pharmacol, 42, 1998, p509–511.
【21】Gelderblom H., Verweij J., Nooter K., Sparreboom A., Eur J Cancer, 37, 2001, p1590-1598.
【22】Zhao C.L., Winnilk M.A., Langmuir, 6, 1990, p514-516.
【23】Molpeceres J., Guzman M., Aberturas M.R., Chacon M., Berges L., Journal of Pharmaceutical Sciences, 85, 1996, p206-213.
【24】Cristine A., Dusica M., Eisenberg A., Colloids and Surfaces：Biointerfaces, 16, 1999, p 3-27.
【25】Zhang N., Guo S., Li H.Q., Liu L., Li Z.H., Gu J. R.,Macromol. Chem. Phys., 207, 2006, p1359-1367.
【26】Shakweh M., Besnard M., Nicolas V., Fattal E., European Journal of Pharmaceutics and Biopharmaceutics, 61, 2005, p1–13.
【27】Saez A., Guzmán M., Molpeceres J., Aberturas M.R.,European Journal of Pharmaceutics and Biopharmaceutics, 50, 2000, p379-387.
【28】Uchegbu I.F., Pharmaceutical Journal, 263, 1999, p309-318.
【29】 Niwa T., Takeuchi H., Hino T., Kunou N., Kawashima Y., Journal of Controlled Release, 25, 1993, p89-98.
【30】Wang J., Wang B.M., Schwendeman S.P., Journal of Controlled Release, 82, 2002, p289-307.