基于RAFT聚合两亲性嵌段聚合物PVP-b-PMMA的制备与应用

发布时间：2018-06-14 11:29

本文选题：RAFT聚合 + 双亲性嵌段共聚物　；参考：《天津工业大学》2016年硕士论文

【摘要】：近年来,用聚合物胶束负载疏水性药物用以解决这类药物差的溶解性的研究越来越多。本文用乙基黄原酸钾和2-溴丙酸乙酯为原料,常温下反应得到小分子链转移剂S-(2-ethyl propionate)-O-ethyl xanthate (CTA),又以甲基丙烯酸甲酯(MMA)、N-乙烯基吡咯烷酮(NVP)为单体,偶氮二异丁腈(AIBN)为引发剂经过两步可逆加成-断裂链转移聚合(RAFT)聚合方法合成了不同MMA含量的双亲性嵌段聚合物PVP-b-PMMA。FT-IR分析了聚合物的结构；1H-NMR分析了聚合物的结构和纯度,比较相应官能团峰值的比例确定出聚合物聚合度,并依此计算出分子量；GPC测试得到聚合物的分子量和分子量分布。用该双亲性的嵌段聚合物与热分解法制备的疏水性的Fe304纳米粒子进行自组装来验证Fe304是否在自组装的过程中进入到胶束的疏水性内腔中,并依此为依据进行下一步载药实验。FT-IR、TGA分析表明新制备的Fe304表面物理吸附和化学键合了一层油胺分子,这层油胺分子使得Fe304的表面变成了疏水性,用来模拟疏水性药物的表面性质。自组装后,TEM表征证明自组装后Fe304能够很好的进入到胶束的内部,并均匀的分散在胶束的内腔中。因此,具备了进行药物载体研究的前提。以芘为探针用荧光色谱法对双亲性嵌段聚合物PVP-b-PMMA进行测试得到该聚合物的临界胶束浓度(CMC,10-4g/L),并且随着MMA链段含量的增加CMC值呈现逐渐降低的趋势。该聚合物与吲哚美辛(IMC)药物在PBS溶液中进行自组装后进行载药量(LC)和包封率(EE)的测试,所测得的载药量为29.5%和包封率为59.0%。体外释放研究表明疏水性的MMA与IMC之间存在的疏水-疏水界面作用力(hydrophobic-hydrophobic interactions)和共价键能(hydrogen bonding)使得PVP-b-PMMA胶束对吲哚美辛的药物缓释达36 h之多。TEM观察了药物释放前和释放后4、8 h的载药胶束的形貌,可以看出药物释放前和释放后的胶束形态几乎无任何变化,因此可以分析出稳定的胶束形貌对IMC的缓释起到了一定的作用。
[Abstract]:In recent years, more and more studies have been done on the solubility of polymer micelles loaded hydrophobic drugs. In this paper, using potassium ethyl xanthate and ethyl 2-bromopropionate as raw materials, a small molecular chain transfer agent S-chl2-ethyl propionate-O-ethyl xanthate was prepared at room temperature, and methyl methacrylate (MMA) -vinylpyrrolidone (NVP) was used as monomer. The amphiphilic block polymer PVP-b-PMMA.FT-IR with different MMA content was synthesized by two-step reversible addition-break chain transfer polymerization (RAFTT) with azodiisobutyronitrile (AIBN) as initiator. The structure and purity of the amphiphilic block polymer PVP-b-PMMA.FT-IR were analyzed by 1H-NMR. The degree of polymer polymerization was determined by comparing the ratio of peak value of functional groups, and the molecular weight and molecular weight distribution of the polymer were calculated by GPC test. The hydrophobic Fe304 nanoparticles prepared by the amphiphilic block polymer and thermal decomposition were self-assembled to verify whether Fe304 entered the hydrophobic cavity of the micelle during the self-assembly process. Based on this, the next drug loading experiment. FT-IRG TGA analysis showed that the newly prepared Fe304 surface was physically adsorbed and chemically bonded with a layer of oleamine molecule, which made the surface of Fe304 hydrophobic. Used to simulate the surface properties of hydrophobic drugs. The TEM characterization of self-assembled Fe304 showed that the self-assembled Fe304 was able to enter the micelle well and dispersed uniformly in the inner cavity of the micelle. Therefore, there is a prerequisite for drug carrier research. The critical micelle concentration of the amphiphilic block polymer PVP-b-PMMA (PVP-b-PMMA) was determined by fluorescence chromatography with pyrene as a probe. The critical micelle concentration of the polymer was 10 ~ (-4) g / L ~ (-1), and the CMC value decreased gradually with the increase of MMA segment content. The polymer and indomethacin IMC) were self-assembled in PBS solution and the drug loading and encapsulation efficiency were tested. The results showed that the drug loading rate and entrapment efficiency were 29.5% and 59.0% respectively. In vitro release studies showed that hydrophobic interaction between hydrophobic MMA and IMC (hydrophobic-hydrophobic interactionsand covalent bonding energy) made the drug release of PVP-b-PMMA micelle to indomethacin as long as 36 h. TEM was used to observe the drug release before and after release. The morphology of the drug-loaded micelles at 4 ~ 8 h after irradiation, It can be seen that there is almost no change in the morphology of the micelles before and after the release of the drug, so it can be found that the stable morphology of the micelles plays a certain role in the sustained release of IMC.
【学位授予单位】：天津工业大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：TQ460.1;O631

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