本文關(guān)鍵詞： L/D-丙氨酸-N-羧基環(huán)內(nèi)酸酐(NCA) 聚乙二醇 聚丙氨酸 藥物釋放　出處：《河北大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：許多抗腫瘤藥物如姜黃素、阿霉素都難溶于水,這極大地限制了它們在臨床治療方面的應(yīng)用。聚合膠束是一種新型的藥物載體,它可用于靶向、水溶性差的治療藥物。膠束具有疏水核心和親水外殼,通過自組裝,兩親性分子或表面活性劑在溶液中聚集成球形或其他結(jié)構(gòu)的納米尺寸膠體顆粒。與通常表面活性劑形成的膠束相比,聚合膠束更穩(wěn)定,并且可以溶解大量疏水性化合物。由于外殼的親水性和外徑的納米尺寸,聚合膠束在腫瘤組織中滯留時間延長,對腫瘤組織具有被動靶向性。因此,設(shè)積、制備不同結(jié)構(gòu)的聚合膠束,探究抗腫瘤藥物的控制釋放與靶向規(guī)律成為當(dāng)今生物醫(yī)學(xué)領(lǐng)域中研究熱點(diǎn)之一。本文主要分為以下幾部分:一、在緒論部分簡要介紹了聚合物膠束以及聚合物膠束的形成機(jī)理、制備方法、載藥以及釋放過程等。二、以L/D-丙氨酸、三光氣為原料,首先合成了L-丙氨酸-N-羧基環(huán)內(nèi)酸酐單體(LA-NCA)和D-丙氨酸-N-羧基-環(huán)內(nèi)酸酐(DA-NCA)單體。以丙氨酸-N-羧基環(huán)內(nèi)酸酐和氨基聚乙二醇單甲醚(MPEG-NH2)分別為單體和大分子引發(fā)劑,成功制備出聚乙二醇-聚丙氨酸嵌段共聚物(PEG-b-PA)。利用紅外光譜、核磁光譜、凝膠滲透色譜對所制備的丙氨酸-N-羧基環(huán)內(nèi)酸酐單體和PEG-b-PA進(jìn)行了結(jié)構(gòu)表征。三、采用透析法制備了基于PEG-b-PA的聚合物膠束,利用透射電子顯微鏡(TEM)觀察了其形貌,聚合物膠束具有球形結(jié)構(gòu)并且粒徑大小均一,其尺寸約為20納米。通過紫外-可見分光光度積測定了不同p H、透析時間、共聚物用量、藥物用量等因素對聚合物膠束載藥與釋放的影響。結(jié)果表明:當(dāng)L-丙氨酸與D-丙氨酸比例為1:0.25,單體與引發(fā)劑比例為70:1,透析時間為72小時時姜黃素的釋放行為為緩釋。
[Abstract]:Many antitumor drugs such as curcumin and adriamycin are insoluble in water which greatly limits their clinical application. Polymeric micelle is a new drug carrier which can be used for targeting. A poorly water-soluble therapeutic drug. Micelles have hydrophobic cores and hydrophilic shells that are self-assembled. Amphiphilic molecules or surfactants aggregate into spherical or other nano-sized colloidal particles in solution, and the polymeric micelles are more stable than those formed by conventional surfactants. Because of the hydrophilicity of shell and the nanometer size of outer diameter, the retention time of polymeric micelles in tumor tissues is prolonged, and the polymer micelles have passive targeting to tumor tissues. The preparation of polymeric micelles with different structures and the investigation of the controlled release and targeting of anti-tumor drugs have become one of the research hotspots in the biomedical field. This paper is mainly divided into the following parts: 1. In the introduction part, the formation mechanism, preparation method, drug loading and release process of polymer micelles and polymer micelles are briefly introduced. Secondly, L / D- alanine and triphosgene are used as raw materials. L- alanine-N-carboxylic anhydride monomers (La-NCA) and D- alanine-N-carboxyl-intracyclic anhydride (DA-NCA) were synthesized. Monomer. The monomer and macromolecular initiator were alanine -N-carboxylic anhydride and amino polyethylene glycol monomethyl ether (MPEG-NH2), respectively. Poly (ethylene glycol) -polyalanine block copolymer (PEG-b-PAA) was successfully prepared. The structure of alanine -N-carboxylic anhydride monomer and PEG-b-PA were characterized by gel permeation chromatography. Thirdly, the polymer micelles based on PEG-b-PA were prepared by dialysis. The morphology of the polymer micelles was observed by transmission electron microscopy (TEM). The polymer micelles have spherical structure and uniform particle size. Its size is about 20 nanometers. Different pH, dialysis time and the amount of copolymers were determined by UV-Vis spectrophotometry. The results showed that the ratio of L- alanine to D- alanine was 1: 0.25 and the ratio of monomer to initiator was 70: 1. The release behavior of curcumin was sustained when dialysis time was 72 hours.
【學(xué)位授予單位】：河北大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：O631;TQ460.1

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本文編號：1489144