pH及温度双重敏感水凝胶的制备与性能研究

采用开环聚合的方法制备了Pluronic/寡聚ε-己内酯嵌段共聚物,该共聚物通过酰氯化反应得到了端基结构为丙烯双键的大分子单体;最后以氧化还原引发剂、采用自由基共聚合方法制备了聚（甲基丙烯酸-co-酰氯化大单体）共聚型水凝胶。性能分析表明所制备水凝胶具有良好的pH和温度双重敏感性。     

SMA的合成与性能研究

本文采用溶液法、本体法和本体-悬浮法制备SMA，考查了单体配比、引发剂浓度、溶剂浓度、聚合温度、反应时间、滴加时间等因素对转化率、反应体系的产品性能的影响。用IR及乌氏黏度计对共聚物进行了表征，同时对反应条件作了初步探讨。     

SMA树脂的合成及性能研究

本文采用一步法和逐步法本体聚合合成苯乙烯Ｓｔ与马来酸酐ＭＡ的共聚体树ＳＭＡ预聚物，该预聚物与玻璃纤维的复合材料的力学性能测试结果证实，随着ＭＡ用量的增加，复合材料的力学性能先增加后下降，这是ＭＡ增加了与纤维的粘结性，降低了分子的韧性的综合表现。     

PDMAEMA的ATRP法合成及其温度/pH敏感性行为研究

采用原子转移自由基聚合法合成了聚甲基丙烯酸-N,N-二甲氨基乙酯(PDMAEMA),研究了聚合物在水中的pH/温度敏感行为。结果表明,当溶液pH值小于聚合物离解常数(pKa)时,聚合物链呈现舒展构象,无相变;当pH值大于pKa时,PDMAEMA发生去质子化作用,部分聚合物析出,且对应的低临界溶解温度值随pH升高而降低。同时,PDMAEMA在水中的平衡溶胀度随pH值增大及温度升高而降低,即PDMAEMA具有明显的pH及温度敏感特性。     

pH敏感高分子水凝胶的合成及性能研究

从分子设计的角度出发,选用具有优良pH敏感的丙烯酸(AAc)为基本原料,制备了pH敏感水凝胶,系统研究了水凝胶的基本物理性能(密度、平均分子量、交联密度、平衡态水含量、固定电荷密度等),测试了水凝胶在不同离子强度下的溶胀、退溶胀性能,并对其响应机理进行了探讨,同时对水凝胶的机械性能进行测试.结果表明:pH敏感水凝胶的机械性能随着pH值增大而变化,其变化幅度最大可达到80%;其机械性能强烈依赖于平衡态溶胀率;离子强度的大小也对水凝胶的机械性能有着决定性影响.     

温度及pH敏感水凝胶的制备与溶胀性能研究

用顺丁烯二酸酐(MAH)对β-环糊精(β-CD)进行化学改性,合成出了一种新型功能性单体MAH-β-CD。以N,N'-亚甲基双丙烯酰胺(BIS)为交联剂,过硫酸铵(APS)为引发剂,通过氧化还原自由基引发单体MAH-β-CD、N-异丙基丙烯酰胺(NIPA)及阴离子单体丙烯酸钠(SA)共聚,合成出一种新型水凝胶。用核磁共振、红外光谱对水凝胶进行了表征。溶胀研究结果表明,该水凝胶具有较好的pH及温度敏感性。     

聚(甲基丙烯酸N,N-二甲氨基乙酯/丙烯酸2-乙基己酯)的温度及pH敏感性能的研究

采用紫外光引发光聚合得到了聚甲基丙烯酸N ,N 二甲氨基乙酯〔P(DMAEMA)〕均聚物和不同组成的聚甲基丙烯酸N ,N 二甲氨基乙酯 /丙烯酸 2 乙基己酯〔P(DMAEMA/EHA)〕共聚物。傅立叶红外光谱和核磁共振氢谱测定了P(DMAEMA/EHA)共聚物的链结构 ,结果表明 :聚合的投料比与所得产物的实际组成比一致。在 pH >8,P(DMAEMA/EHA)共聚物溶液的低临界溶液温度 (LCST)随聚合物中EHA组分的增加逐渐下降 ;在pH≤ 8时 ,则观测不到体系的LCST。 37℃下均聚物及共聚物试样 (D、D/E1、D/E2、D/E3)的pH敏感点分别为8 80 ,8 72 ,8 37,8 2 9。共聚物结构中EHA组分越多 ,则 pH敏感点越低。P(DMAEMA)均聚和共聚物的LCST随着NaCl浓度的升高而线性下降 ,且下降的速率相等。     

新型P(NIPAAm-co-IA)pH敏感智能水凝胶的合成与性能研究

采用溶液共聚法合成了聚(N-异丙基丙烯酰胺-co-衣康酸)(P(NIPAAm-co-IA))pH敏感性阴离子型水凝胶.通过正交设计实验研究了共聚单体比值、单体浓度、交联剂用量、引发剂用量等因素对凝胶性能的影响,分析了各因素的影响程度和最优工艺条件,结果显示,在所考察的范围内,最优工艺条件为:n(IA):n(NIPAAm...     

Synthesis of pH-sensitive hollow polymer microspheres with movable magnetic core

The pH-sensitive hollow poly(N,N′-methylenebisacrylamide-co-methacrylic acid) (P(MBAAm-co-MAA)) microspheres with movable magnetic/silica (Fe₃O₄/SiO₂) cores were prepared by the selective removal of poly(methacrylic acid) (PMAA) layer in ethanol/water from the corresponding Fe₃O₄/SiO₂/PMAA/P(MBAAm-co-MAA) tetra-layer microspheres, which were synthesized by the distillation precipitation copolymerization of N,N′-methylenebisacrylamide (MBAAm) and methacrylic acid (MAA) in the presence of Fe₃O₄/SiO₂/PMAA tri-layer microspheres as seeds in acetonitrile with 2,2′-azobisisobutyronitrile (AIBN) as the initiator. The Fe₃O₄/SiO₂/PMAA tri-layer microspheres were afforded by the distillation precipitation polymerization of MAA with 3-(methacryloxy)propyl trimethoxysilane (MPS)-modified Fe₃O₄/SiO₂ core-shell particles as the seeds. The functional multi-layer inorganic/polymer microspheres and the corresponding hollow polymer microspheres with movable magnetic cores were characterized with transmission electron microscopy (TEM), Fourier-transform infrared (FT-IR) spectra, dynamic light scattering (DLS), and vibrating sample magnetometer (VSM).     

基于pH敏感型葡聚糖水凝胶微球的药物载体

以葡聚糖为原料,采用反相微乳液技术制备了一种含有席夫碱结构的葡聚糖基水凝胶纳米微球作为载体,通过交联剂聚乙烯亚胺(PEI)的静电吸附作用对药物模型8-羟基芘-1,3,6-三磺酸三钠盐(HPTS)进行了包埋,利用FTIR、SEM和DLS等对微球的结构和形貌进行了表征。结果表明,这种葡聚糖纳米水凝胶载药前后均具有良好的球形结构,平均粒径分别在459和648 nm左右。载药效果及药物释放行为研究发现,该葡聚糖纳米水凝胶可对HPTS进行有效负载,且其释放行为具有明显的酸性环境敏感性,酸性越强,释放越快。含有席夫碱结构的葡聚糖纳米凝胶微球可作为pH敏感型载体应用于药物递送领域。     

Synthesis and characterization of an amphiphilic graft polymer and its potential as a pH-sensitive drug carrier

The synthesis and properties of a new pH-sensitive polymer Poly(?-caprolactone) Grafted Poly(ethylene glycol) Based Poly(ß-amino ester) (PEGAE-g-PCL) are described here. The successful synthesis of the graft copolymer was confirmed by ¹H NMR. The self-assemble behavior of the amphiphilic polymer was investigated using pyrene as a probe. Dynamic light scattering (DLS) showed that the polymeric micelles had a size of 60 nm at physiological pH and were responsive to pH. A spherical morphology was observed for the micelles using transmission electron microscopy (TEM). Zeta-potential measurement at different pH showed that the micelles were neutral at pH 7.4 and positively charged at lower pH. Doxorubicin (DOX) was used as a model drug and loaded in the micelles. The drug loaded micelles showed a slow and pH-dependant drug release behavior. The remaining hydroxyl groups on the main chain made it possible the further conjugation of imaging agents or targeting groups.     

Synthesis of pH-sensitive hollow polymer microspheres and their application as drug carriers

The pH-sensitive hollow poly(N,N′-methylene bisacrylamide-co-methacrylic acid) (P(MBAAm-co-MAA)) microspheres were prepared by a two-stage distillation precipitation polymerization to afford a core-shell poly(methacrylic acid)/poly(N,N′-methylene bisacrylamide-co-methacrylic acid) (PMAA/(P(MBAAm-co-MAA))) microsphere with subsequent removal of poly(methacrylic acid) (PMAA) core. PMAA/P(MBAAm-co-MAA) core-shell microspheres were synthesized by the second-stage copolymerization of N,N′-methylene bisacrylamide (MBAAm) as crosslinker and the functional methacrylic acid (MAA) comonomer in acetonitrile with 2,2′-azobisisobutyronitrile (AIBN) as initiator. The pH-responsive properties of hollow P(MBAAm-co-MAA) microspheres were investigated by dynamic laser scattering (DLS). The loading and controlled-release behavior of the drug for hollow P(MBAAm-co-MAA) microspheres was strongly dependent on the pH values with doxorubicin hydrochloride (DXR) as a model molecule. The core-shell and hollow polymer microspheres were characterized by transmission electron microscopy (TEM), Fourier-transform infrared spectra (FT-IR), DLS and elemental analysis.     

疏水改性羧甲基纤维素及其pH敏感水凝胶的研究

通过羧甲基纤维素钠( CMC -Na)与脂肪酰氯在正庚烷介质中酯化反应制备疏水改性羧甲基纤维素(Ln-CMC -Na),讨论了物料比、温度和时间对反应的影响,确定了适宜的反应条件.根据Ln-CMC -Na的水溶性,确定在脂肪酰氯与CMC -Na摩尔比为0.08时,分别用十、十二、十四、十六和十八酰氯制备出系列改性产品,并测定了其HLB值、表面张力和临界胶束浓度.以三氯化铝为交联剂,Ln-CMC -Na作配体制得pH敏感水凝胶.     

快速溶胀pH敏感明胶水凝胶的研究

明胶具有生物降解性及良好的生物相容性,已被广泛用于照相、食品及医药工业。为开发明胶的新用途,用乙二胺四乙酸酐(EDTAD)成功地对明胶进行了乙酰化改性,研制出了酰化明胶水凝胶,用紫外-可见分光光度法确定了酰化反应的工艺条件为:调节w(明胶)=1%水溶液的pH到12,在室温下反应2~3 h。酰化后明胶溶液的等电点向低pH方向移动,改性明胶所生成的水凝胶达到溶胀平衡所需的时间大幅度减小,平衡溶胀率呈几十甚至几百倍提高,且当m(EDTAD)∶m(明胶)<1∶15时,随着酰化剂用量的增加,改性明胶水凝胶的平衡溶胀率最高可达110左右。且水凝胶具有pH敏感性和离子强度敏感性,pH敏感点为pH≈4。     

A pH-sensitive micelle for codelivery of siRNA and doxorubicin to hepatoma cells

Aiming to effectively codeliver chemotherapeutic drugs (DOX) and siRNA (BCL-2 siRNA) into tumor cells, well-defined triblock copolymers composed of hydrophilic and hydrophobic blocks were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. The poly(ethylene glycol) (PEG) macroRAFT agent and two pH-sensitive monomers (2-(diethylamino)ethyl methacrylate, DEA and 2-(dimethylamino)ethyl methacrylate, DMA) were used for synthesizing the copolymers consisting of pH-sensitive PDEA, PDMA and PEG blocks. At pH 10, the copolymer in aqueous solution self-assembled into a micelle with hydrophobic core consisting of PDEA and PDMA for doxorubicin (DOX) encapsulation, owing to the deprotonation of the side tertiary amino groups. At neutral pH, the hydrophobic core became porous and positively charged to allow siRNA complexation due to PDMA solubilization (the pK_a of PDMA is around 8.0). Inside the acidic lysosomal compartments, PDEA was protonated and thus became hydrophilic to result in rapid release of DOX. Moreover, existence of two pH-sensitive blocks PDMA and PDEA endowed the copolymer with proton buffering effect that facilitated lysosomal escape of nanocomplex and siRNA release inside cells. Our results showed that the two codelivered therapeutic agents acted synergistically on the human hepatic carcinoma HepG2 cells to induce apoptosis in a highly effective manner.     

三羟甲基丙烷酯的合成及其抗乳化性能研究

以三羟甲基丙烷(TMP)及不同类型的脂肪酸为原料，合成了具有抗乳化性能的三羟甲基丙烷酯系列产品。考察了该系列产品抗乳化性能，确定了具有较佳的抗乳化性能的产品配方：即用油酸-庚酸-己二酸组合与TMP反应，当n(TⅧ)／n(混酸)=1／2．9，m(油酸)／m(庚酸 油酸)=80％，n(油酸 庚酸)／n(己二酸)=6时，所得复合酯具有较好的抗乳化性能。     

pH敏感性生物基纳米载药粒子的研究进展

生物基来源的聚合物具有生物相容性高、无毒易降解等优势,近些年来作为药物载体在生物医药领域受到了广泛的关注。人体内的生理环境存在pH差异,利用pH作为刺激响应的信号,可以赋予聚合物纳米载药系统理想的靶向释药性能。本综述着眼于pH敏感性的生物基聚合物纳米粒子,揭示了纳米载药粒子中化学键断裂与质子化作用两种pH响应的控释机制,并针对两者的控释特点进行了分析总结。在此基础上,介绍了几种生物基药物载体的pH控释研究及其在生物医药领域的应用进展,并提出了目前利用各种生物基材料作为药物载体存在的问题。最后,针对目前存在的载药量低、敏感性不强等问题,提出了可采用多种方式联合载药、多重刺激响应结合等方式进行深入研究的展望。     

Temperature- and pH-sensitive membrane formed from blends of poly(vinylidene fluoride)-graft-poly(N-isopropylacrylamide) and poly(acrylic acid) microgels

Temperature- and pH-responsive membranes prepared from blends of poly(vinylidene fluoride)-graft-poly(N-isopropylacrylamide)(PVDF-g-PNIPAM) copolymer and poly(acrylic acid) (PAA) microgels in N,N-dimethylformamide (DMF) solution by phase inversion method. PAA microgels help PNIPAM chains largely enrich onto membrane surface. Furthermore, adding PAA microgels increases the porous size, porosity and hydrophilic property of the blend membrane. The membranes show temperature-sensitivity between 30 and 35 °C, and pH-sensitivity between pH 3 and 5 on permeating aqueous solutions. Meanwhile, the blend membranes keep good antifouling property even if one of the hydrophilic components becoming hydrophobic in response to temperature or pH stimuli, which is superior to single-sensitive PVDF membrane.