標的導向型磁性免疫中空藥物載體之製備與研究

Abstract

本論文以甲基丙烯酸甲酯(methyl methacrylate，MMA)與甲基丙烯酸 (methacrylic acid,MAA)為單體，以無乳化劑乳化聚合方式進聚合反應，合成出具有COOH官能基且未交聯結構的Poly(MMA-MAA)乳膠顆粒後，並以此顆粒為核，加入氮-異丙基丙烯醯胺(N-isopropylacrylamide，NIPAAM)及MAA單體，N,N'-methylenebisacrylamide (MBA) 為交聯劑，以無乳化劑乳化聚合方式合成出具備溫度敏感性的Poly (MMA-MAA) /(NIPAAM-MAA)核¬¬殼乳膠顆粒 ，在聚合反應中變化NIPAAM及MAA的比例、交聯劑量下利用TEM進行顆粒形態的觀察。接著我們以氨水將Poly (MMA-MAA)/ (NIPAAM-MAA) 核殼乳膠顆粒內部的Poly(MMA-MAA)溶解出來，形成中空顆粒，改變溶解的溫度與時間，以TEM觀察顆粒形態之變化，探討NIPAAM/MAA比例以及溫度、時間對於溶解核層Poly(MMA-MAA)的影響。 接著進行磁性乳膠顆粒的製備實驗，合成出具有羧酸基的Poly (MMA-MAA)/ (NIPAAM-MAA)乳膠顆粒，利用乳膠顆粒的羧酸基與鐵離子先鍵結成-COOFe2+及-COOFe3+，再加入氨水，當氨水參與反應使環境變為鹼性時，Fe3O4會以in-situ的方式形成，便合成出中空型磁性乳膠顆粒。 最後以磁性中空乳膠顆粒為seed，再添加MAA、NIPAAM與交聯劑MBA，添加起始劑後使中空型磁性乳膠顆粒外再包覆一層具有交聯結構的Poly(NIPAAM-MAA)，形成Poly(NIPAAM-MAA)/Fe3O4 / Poly(NIPAAM-MAA)中空型磁性乳膠顆粒，接著進行LCST與TEM的測試與觀察。

In our study, we synthesize the linear copolymer of MMA (methyl methacrylate) and MAA (methacrylic acid) which has carboxyl groups. Then we use Poly(MMA-MAA) as a seed, adding different amount of crosslinker and different ratio of NIPAAM (N-isopropylacrylamide)/MAA (methacrylic acid) to synthesize Poly(MMA-MAA)/(MAA-NIPAAM) copolymer. We use ammonium hydroxide to dissolve Poly(MMA-MAA) to get hollow Poly(NIPAAM-MAA) latex at different temperature and span. We use transmission electron microscopy、UV-vis SpectropHotometer to observe hollow Poly(MAA-NIPAAM) latex . Then synthesizing the magnetic hollow latex, we use different method synthesizing it from the traditional method. First, we synthesize the hollow latex. Second, using the functional group(-COOH) on the hollow latex surface to bond Fe2+ and Fe3+. Finally, we put ammonium hydroxide into the latex, and we can get magnetic hollow latex by im-situ method. Final step is to synthesize Poly(MAA-NIPAAM)/Fe3O4/A(MAA-NIPAAM) magnetic hollow latex . We adding different ratio of NIPAAM/MAA and different amount of initiator and crosslinker into Poly(MAA-NIPAAM)/Fe3O4 latex to synthesize Poly(MAA-NIPAAM)/Fe3O4/A(MAA-NIPAAM) magnetic hollow latex. Then we use transmission electron microscopy、UV-vis SpectropHotometer to observe property of Poly(MAA-NIPAAM)/Fe3O4/A(MAA-NIPAAM) magnetic hollow latex.