温度和pH双重敏感荧光复合微凝胶制备和表征

通过反相悬浮聚合法制备N-异丙基丙烯酰胺(NIPAM)和甲基丙烯酸(MAA)的共聚微凝胶P(NIPAM-co-MAA), 以其为模板, 利用3-氨丙基三乙氧基硅烷(APTES)在碱性条件下的水解缩合反应, 制备得到了由氨基修饰的P(NIPAM-co- MAA)/SiO₂高分子/无机复合微凝胶, 再通过异硫氰酸荧光素(FITC)与氨基的键和作用, 得到了具有核-壳结构的温度和pH双重敏感荧光复合微凝胶. 通过扫描电子显微镜(SEM)、傅立叶变换红外光谱(FT-IR)、热台偏光显微镜(POM)和共聚焦激光扫描显微镜(CLSM)等手段对复合微凝胶进行了结构和性质表征, 结果表明, 该复合微凝胶对温度和pH均具有良好的响应特性, 并在可见光激发下发出荧光.     

壳聚糖大分子链的形态调控及其在微悬浮聚合中的分散稳定作用

以易去除可回用的壳聚糖(CS)为分散剂,通过微悬浮聚合制备微米级的软硬质聚合物胶粒.考察不同酸碱度下水相介质中CS大分子链的质子化程度、亲疏水性和形态结构,及其对油水界面处CS存在形态的影响,进而评估其对剪切均质化所制单体液滴的分散稳定作用.发现通过调节体系pH值可较容易地控制CS大分子链的质子化程度、亲疏水性以及在单体液滴表面的吸附效率和铺展程度,进而可在弱酸性环境下调控微悬浮聚合体系中CS的分散能力和稳定效果.特别是当pH值在6.0左右时,CS大分子链质子化程度和亲疏水性适中,链内易形成具有一定内聚密度的高分子链收缩构象、链间易形成由多根CS链缠结而成的疏松聚集状态.在此状态下的CS链对苯丙单体液滴具有较强的分散能力和稳定作用,因而通过微悬浮聚合可制得形态结构规整、分散状态良好的聚合物粒子.进一步与微悬浮聚合常用的无机粉末类和高分子类分散剂进行应用效果比较,发现CS具有形态调控性好、分散稳定效率高、易去除能回用、特别适合制备软质微米胶粒等优点,是一种有别于无机粉末类和高分子类分散剂的新型微悬浮聚合分散剂.     

温度敏感型阳离子聚丙烯酰胺微球的制备及表征

以丙烯酰胺与甲基丙烯酰氧乙基三甲基氯化铵为单体,偶氮二异丁基脒二盐酸盐为引发剂,聚丙烯酰氧乙基三甲基氯化铵为稳定剂,在乙醇和水的混合介质中采用分散聚合的方法制备具有温度敏感性的阳离子型聚丙烯酰胺水分散微球。利用1HNMR和FTIR对共聚物的结构进行了表征,与此同时采用光学显微镜、TEM、激光粒度仪对聚合物微球的形貌、粒径等进行了系统研究。结果表明,随着醇水比的降低,微球的粒径逐渐减小,特性粘数逐渐增加;随着稳定剂浓度的增加,微球粒径逐渐减小。对阳离子型聚丙烯酰胺水分散微球的变温紫外研究结果表明,分散液具有明显的温敏性。随着温度在5～50℃范围内变化,分散液呈现从乳白色到透明状态的可逆变化。这是由于分散液微球的粒径随温度变化而发生可逆变化的结果。     

温敏性微凝胶的研究技术

温敏性微凝胶因具有尺寸小、对温度的变化响应速度快、渗透性好等优点,所以在许多领域显示出良好的应用前景.温敏性微凝胶的应用性能取决于由其结构所决定的物理化学性能.为了深入了解温敏性微凝胶的结构与性能关系,研究人员利用不同技术手段进行了广泛研究.本文主要综述了显微技术、示差扫描量热技术、光散射技术、中子散射技术、核磁共振及荧光光谱等在温敏性微凝胶结构与性能研究中的应用、主要研究结果,并对微凝胶未来的研究方向提出了一些建议.     

单分散CdS纳米晶/PNIPAM复合水凝胶的制备及其温敏荧光特性

采用液体-固体-溶液法(LSS)制备单分散CdS纳米晶;通过自由基聚合制备单分散CdS纳米晶/聚N-异丙基丙烯酰胺(CdS/PNIPAM)复合温敏水凝胶.采用HRTEM、XRD、FTIR、DSC、PL等对CdS纳米晶、CdS/PNIPAM温敏复合凝胶的微观结构与性能进行了表征,变温荧光光谱研究了温度对凝胶荧光性能的影响.结果表明,CdS纳米晶粒径约为2.8 nm,单分散性良好;复合凝胶的荧光发射强度与环境温度存在一定的关联性,且呈可逆性.     

浊度法表征温敏性微凝胶体积的相转变行为

以N-异丙基丙烯酰胺(NIPAM)、甲基丙烯酸(MAA)为单体,N,N-亚甲基双丙烯酰胺(MBA)为交联剂,制备了温敏性聚(N-异丙基丙烯酰胺)(PNIPAM)和具有温度、pH敏感性的聚(N-异丙基丙烯酰胺-co-甲基丙烯酸)(PNIPAM-MAA)微凝胶。通过测定不同温度和pH条件下微凝胶浊度变化,表征微凝胶的温度及pH敏感性,描述了NaCl浓度和pH对微凝胶体积相转变温度的影响。同时,测定了微凝胶的临界聚沉浓度及临界絮凝温度,表征了微凝胶的稳定性,讨论了影响微凝胶的稳定性因素。     

新型温敏羟丙基纤维素微凝胶的合成

天然高分子具有良好的生物相容性和生物可降解性,因此用天然高分子制备的微凝胶更适合于生物医学领域的应用。羟丙基纤维素(HPC)是一种具有温度敏感性的纤维素衍生物,可通过不同的方法制备为微凝胶,然而现有方法制备的HPC微凝胶都不能完全降解。我们采用一种新方法制备HPC微凝胶。首先通过NaIO4处理将醛基引入HPC。红外光谱检测证明了醛基的生成。氧化后的HPC仍具温敏性,其最低临界溶解温度(LCST)保持不变;当加热到LCST以上时,HPC分子通过疏水相互作用聚集成纳米小球;再加入交联剂己二酸二酰肼,通过醛基与胺基之间的反应,使纳米小球共价交联得到HPC微凝胶。电镜研究表明HPC微凝胶呈球形,粒径在100～300nm之间。浊度和光散射研究表明HPC微凝胶仍具温敏性。细胞毒性实验表明我们制备的微凝胶几乎没有细胞毒性。由于HPC及交联剂己二酸二酰肼均可生物降解,预期我们制备的微凝胶也能很好地降解,并有望应用于生物医学领域。     

含自由氨基酸侧链的温敏性微凝胶的制备及性能

采用无皂乳液聚合法使N-异丙基丙烯酰胺(NIPAM)、ε-丙烯酰基-L-赖氨酸(εACRLLY)和N,N-亚甲基双丙烯酰胺(BA)交联共聚,制备了含有自由氨基酸侧链的温敏性微凝胶.利用透射电子显微技术(TEM)、动态光散射技术(DLS)及浊度法对所制备的微凝胶的形态及相转变进行了表征.TEM结果表明,所得的微凝胶具有规则的球型形态,微凝胶的粒径随εACRLLY含量的增加而减小.DLS及浊度结果表明,微凝胶粒径呈单分散的窄分布,随着温度的升高,微凝胶粒径减小,有着明显的体积相转变温度(VPTT);亲水单体εACRLLY的引入能够有效地调节共聚物微凝胶的VPTT,并且VPTT随εACRLLY含量的增加几乎呈线性上升.微凝胶在对盐酸阿霉素的药物释放研究表明,所制备的微凝胶在20℃,12 h内释放了56%,37℃下释放了73%;37℃,pH=7.4下13 h内释放73%,pH=4.5下基本释放完毕,该微凝胶表现出良好的药物缓释性能.     

葡萄糖敏感微凝胶的溶胀动力学研究

通过沉淀聚合法合成了P(NIPAM-co-AA)微凝胶,然后在EDC催化下用3-氨基苯硼酸对微凝胶进行改性,制备了P(NIPAMI-co-AAPBA)微凝胶.红外光谱检测证明改性完全.改性后的微凝胶仍具有很好的温敏性,但由于引入疏水的苯硼酸基团,微凝胶的体积相转变温度大大降低.P(NIPAM-co-AAPBA)微凝胶具...     

改进的微悬浮聚合法制备聚合物微球

微悬浮聚合法是制备聚合物微球的方法之一,它是先将单体相分散为一定粒度的微液滴,再在低速搅拌(75～100r/min)下进行聚合反应~[1,2],对聚合设备无特殊要求,且避免了悬浮聚合法制备微球时连续数小时的高速搅拌~[3],只要有合适的均化器即可大批量制备1～50μm的聚合物微球,且可适当控制粒度.但由于一般单体在分散介质中均有一定的溶解性,且液滴粒径越小单体溶解度越大,致使聚合过程中单体可通过介质扩散而产生单体在不同粒     

α-环糊精准轮烷/N-异丙基丙烯酰胺交联共聚温敏型超分子结构水凝胶的制备与表征

采用一锅法合成了甲基丙烯酰基封端的聚乳酸-聚乙二醇-聚孔酸(PLA-PEG-PLA)三嵌段大分子单体,然后再通过与α-环糊精进行超分子自组装,得到聚准轮烷.将制备的聚准轮烷悬浮在N-异丙基丙烯酰胺水溶液中,再加入适量的光引发剂,在紫外光的照射下,溶液快速固化,得到了具有超分子结构的温敏型凝胶体.采用FTIR、TG、XRD等分析手段对所得聚准轮烷及其水凝胶进行了表征.     

Thermosensitive phase behavior and drug release of in situ gelable poly(N-isopropylacrylamide-co-acrylamide) microgels

In situ gelable poly(N-isopropylacrylamide-co-acrylamide) microgels were prepared by precipitation polymerization in the presence of various amounts of N,N′-methlenebisacrylamide as a crosslinker. The diameters of microgels were in the range of 200–300 nm with narrow distributions as determined by photo correlation spectroscopy. The equilibrium swelling ratio and thermosensitive properties of the microgels increased with decreasing crosslinker content. The volume phase transition of microgels dispersions at high concentrations were investigated by phase diagrams. The microgels dispersions experienced four phases when the temperature was increased: semitranslucent swollen gel, clear flowable suspension, cloud flowable suspension, and white shrunken gel. The related phase transition temperatures were influenced by crosslinker content and the concentration of the microgel dispersions. Herein, the gelation temperature was changed by more than 20 °C, shrinking temperatures were slightly changed by about 3 °C, and cloud point temperatures showed almost no change. The three phase transition temperatures of microgels dispersed in phosphate-buffered saline solutions were lower than that in water. As drug carriers, the release rates of bleomycin from bleomycin-loaded microgel dispersions exhibited diffusion control at human body temperature.     

Synthesis and characterization of thermosensitive PNIPAM microgels covered with superparamagnetic gamma-Fe2O3 nanoparticles

In the present study we report a facile and reproducible method of preparing magnetic thermosensitive hybrid material based on P(NIPAM) microgels covered with gamma-Fe2O3 nanoparticles of 6-nm size. The iron oxide nanoparticles provided magnetic response to the microgels. In addition, the presence of the magnetic nanoparticles on the microgels altered their swelling behavior and shifted their volume phase transition temperature to higher values. In particular, for inorganic shells with 18% (w/w) of magnetic nanoparticles the volume phase transition of the microgels was shifted from 36 to 40 degrees C. In contrast, for shells consisting of 38% (w/w) magnetic nanoparticles the volume phase transition of the microgels was almost blocked, thus indicating that the microgel thermal response was strongly affected by the presence of the inorganic nanoparticles. The synthesized thermosensitive magnetic microgels are envisaged to be ideal for potential applications as thermosensitive targeted drug delivery systems.     

Hydroxyl functionalized thermosensitive microgels with quadratic crosslinking density distribution

N-isopropylacrylamide (NIPA) based uniform thermosensitive microgels were synthesized by dispersion polymerization by using relatively hydrophilic crosslinking agents with hydroxyl functionality. Glycerol dimethacrylate (GDMA), pentaerythritol triacrylate (PETA) and pentaerythritol propoxylate triacrylate (PEPTA) were used as crosslinking agents with different hydrophilicities. A protocol was first proposed to determine the crosslinking density distribution in the thermosensitive microgel particles by confocal laser scanning microscopy (CLSM). The microgels were fluorescently labeled by using hydroxyl group of the crosslinking agent. The CLSM observations performed with the microgels synthesized by three different crosslinking agents showed that the crosslinking density exhibited a quadratic decrease with the increasing radial distance in the spherical microgel particles. This structure led to the formation of more loose gel structure on the particle surface with respect to the center. Then the use of hydrophilic crosslinking agents in the dispersion polymerization of NIPA made possible the synthesis of thermosensitive microgels carrying long, flexible and chemically derivatizable (i.e., hydroxyl functionalized) fringes on the surface by a single-stage dispersion polymerization. The microgels with all crosslinking agents exhibited volume phase transition with the increasing temperature. The microgel obtained by the most hydrophilic crosslinking agent, GDMA exhibited higher hydrodynamic diameters in the fully swollen form at low temperatures than those obtained by PETA and PEPTA. Higher hydrodynamic size decrease from fully swollen form to the fully shrunken form was also observed with the same microgel.     

核壳结构葡萄糖敏感微凝胶的制备

用先合成聚N-异丙基丙烯酰胺(PNIPAM)微凝胶核再包一层N-异丙基丙烯酰胺/丙烯酸共聚物(P(NIPAM-co-AA))壳的办法合成了一系列核壳结构微凝胶.微凝胶壳层厚度随投入的壳储备溶液的增加而增加.研究了pH=3.5时核壳微凝胶的温敏体积相转变行为.由于PNIPAM核和P(NIPAM-co-AA)壳的相转变温度很接近,因此只观察到一个相转变.在EDC催化下使3-氨基苯硼酸与壳层中的羧基反应,将苯硼酸基(PBA)引入微凝胶,得到核为PNIPAM、壳为P(NIPAM-co-AMPBA)的核壳结构微凝胶.改性后的微凝胶表现出3个体积相转变过程.其中第一个对应于P(NIPAM-co-AMPBA)壳层的体积相转变.第二和第三个则是PNIPAM核的相转变过程.由于在沉淀聚合时交联剂BIS反应性更大,PNIPAM核结构不均一,形成BIS含量高的"核"和BIS含量低的"壳".BIS含量低的"壳"被一层疏水的P(NIPAM-co-AMPBA)壳包裹,拉大了其与"核"的相转变温度的差别,因此随着温度升高表现出两个相转变过程.PBA改性的微凝胶同样表现出葡萄糖敏感性,但在葡萄糖存在下溶胀度的改变较小.     

The volume transition in thermosensitive core–shell latex particles containing charged groups

An investigation of the volume transition in thermosensitive core–shell particles by dynamic light scattering (DLS) is presented. The core of the particles consists of polystyrene (diameter 118 nm), whereas the thermosensitive shell is composed of a network of poly (N-isopropylacrylamide) containing 2 mol% acrylic acid counits. The hydrodynamic radius of these particles as determined by DLS decreases in a continuous manner when raising the temperature. It is shown that the volume transition in the core–shell microgels remains continuous for a wide range of ionic strengths and pH values. This behavior is opposite to that of macrogels of the same chemical composition, which undergo a discontinuous volume transition. The present investigation therefore demonstrates that affixing the network to solid colloidal particles profoundly alters the volume transition of thermosensitive networks. The reason is that shrinking can take place only along the radial direction of the particles. The solid core thus exerts a strong spatial constraint onto the network, which leads to the observed behavior. Received: 29 March 1999 Accepted in revised form: 16 July 1999     

Unperturbed volume transition of thermosensitive poly-(N-isopropylacrylamide) microgel particles embedded in a hydrogel matrix

The thermoresponsive behavior of poly-(N-isopropylacrylamide) (PNiPAM) microgels embedded in a covalently cross-linked polyacrylamide hydrogel matrix was investigated using ultraviolet-visible (UV-vis) spectroscopy, small-angle neutron scattering (SANS), and confocal laser scanning microscopy. The hydrogel synthesis was performed at two different temperatures, below and above the volume phase transition temperature of PNiPAM, resulting in highly swollen or fully collapsed PNiPAM microgel particles during the incorporation step. UV-vis spectroscopy experiments verify that the incorporation of thermosensitive microgels leads to temperature-sensitive optical properties of the composite materials. SANS measurements at different temperatures show that the thermosensitive swelling behavior of the PNiPAM microgels is fully retained in the composite material. Volume and structure criteria of the embedded microgel particles are compared to those of the free microgels in acrylamide solution. To visualize the temperature responsive behavior of larger PNiPAM particles, confocal fluorescence microscopy images of PNiPAM beads, of 40-microm size, were taken at two different temperatures. The micrographs also demonstrate the retained temperature sensitivity of the embedded microgels.     

Preparation of a thermosensitive and biodegradable microgel via polymerization of macromonomers based on diacrylated Pluronic/oligoester copolymers

A novel biodegradable and thermosensitive hydrogel microparticle was prepared via suspension polymerization of a kind of block copolymer macromonomers. According to the molecular design, the macromonomer is composed of a thermosensitive triblock copolymer poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) and two oligomers of biodegradable polyester such as oligo(lactic acid) or oligo(ε-caprolactone), and end-capped with acryloyl groups. Microgels were obtained by inverse suspension polymerization of the macromonomer aqueous droplets initiated by a redox initiator. Thermosensitivity and in vitro biodegradation of the resultant microgels were confirmed. The gel microparticles in an aqueous solution were swollen at low temperature and shrunken at high temperature (human body temperature). Degradation rate could be adjusted by controlling the composition and the degree of polymerization of oligoester. Thus, the microgels exhibit combinatory and tunable properties.     

基于互穿网络结构的pH/温度双重刺激响应性微凝胶的研究

室温下采用氧化-还原引发体系,以低交联密度的聚(N-异丙基丙烯酰胺)(PNIPAM)微凝胶为种子,通过种子乳液聚合法合成由PNIPAM和聚丙烯酸(PAA)形成的具有互穿聚合物网络结构的微凝胶.傅立叶变换红外光谱分析结果表明微凝胶由PNIPAM和PAA两种聚合物组成,透射电镜表征结果证实微凝胶中PNIPAM和PAA两种聚合物形成了互穿网络结构.用动态激光光散射测试不同温度或pH值水介质中微凝胶的粒径,结果发现微凝胶具有良好的pH/温度双重刺激响应性.在水介质pH值大于5.5的情况下,PAA组分对微凝胶的体积相转变温度没有影响;而在水介质pH值为4.0的情况下,由于PAA与PNIPAM之间的氢键作用,微凝胶的体积相转变温度稍微降低.微凝胶中PAA组分含量越高,其pH刺激响应性越显著.