双硒葡聚糖水凝胶的合成及其药物释放行为

首先,通过双硒化钠(Na2Se2)与11-溴-1-十一醇的亲核取代反应合成了一种二羟基二硒化物;然后,通过该二硒化物与异佛尔酮二异氰酸酯(IPDI)反应合成了一种异氰酸根封端的双硒交联剂;最后,通过葡聚糖与该交联剂的反应合成了一种含双硒键的葡聚糖水凝胶。采用核磁共振氢谱(~1H-NMR)、傅里叶红外光谱(FT-IR)、凝胶渗透色谱(GPC)、拉曼光谱(Raman)、旋转流变仪(Rheology)、紫外-可见分光光度计(UV-Vis)等表征方法研究了产物的结构、溶胀性能、氧化响应行为、流变性能和体外药物释放行为。结果表明:含双硒键的葡聚糖水凝胶具有氧化响应能力;在没有氧化刺激条件下,该水凝胶24h的累积药物释放量为45%左右,而在氧化刺激条件下(w(H_2O_2)=0.2),只需14h便可释放90%的负载药物。     

光响应性微凝胶的分子设计和智能材料构筑

微凝胶能够在外界刺激下改变自身尺寸,是一类重要的智能材料构筑基元。光刺激具有可远程控制、能快速切换等特点,在刺激响应性材料的设计中受到了广泛关注。将光刺激响应性基元引入到微凝胶体系,可以得到一系列具有重要应用前景的智能材料。本文综述了近年来光响应微凝胶的研究进展,总结了赋予微凝胶光响应性的四种分子设计,包括光致异构化型、光致生热型、光致(解)交联型、光致生酸型;介绍了光响应微凝胶在调光材料、药物控释、信息显示和自修复凝胶等领域的应用;展望了该领域的研究方向、发展和应用前景。     

聚合物微凝胶研究进展

微凝胶是一种具有交联网络结构的聚合物胶体粒子,处于良好溶剂中的刺激响应型微凝胶会受某些外界环境的刺激,产生溶胀-消溶胀响应行为,具有快速、可逆的相变特性和较好的生物相容性。本文综述了近年来国内外微凝胶的研究现状,介绍了互穿网络型、核-壳型和含有纳米粒子的复合型微凝胶的结构、特性和制备方法,阐述了微凝胶在药物控制释放、催化反应体系、生物传感器等方面的应用,探讨了聚合物微凝胶领域的研究前景和所面临的问题。     

微凝胶胶体晶体研究进展

Poly(N-isopropylacrylamide)(PNIPAM)微凝胶粒子是一种软的胶体粒子.和单分散的SiO_2、PS、PMMA等硬的胶体粒子一样,单分散的PNIPAM微凝胶粒子也可以自组装成为高度有序的胶体晶体.微凝胶粒子软物质的特性及其对外部刺激的响应性赋予其不同于硬球的组装行为.微凝胶胶体晶体的高度有序结构及其刺激响应性使其在诸多领域有重要用途.本文分别介绍了三维及二维微凝胶胶体晶体组装的研究进展,并对已开发的基于微凝胶胶体晶体的应用进行了总结.     

pH 响应P(AM-co-AA)/PAAC 半互穿网络微凝胶的合成及表征

在反相微乳液体系中,合成了 pH 响应的聚丙烯酰胺(AM)-丙烯酸(AA)/聚烯丙基氯化铵(PAAC)半互穿网络(semi-IPN-P(AM-co-AA)/PAAC)微凝胶.采用 TEM、光散射及 Zeta电位对微凝胶的微观形貌及 pH 的响应行为进行测定,考察离子强度对微凝胶粒径的影响.结果表明:微凝胶的粒径约 80 nm,溶胀行为对pH及离子强度敏感,改变PAAC的含量可以得到不同PH 下响应的微凝胶.     

温敏型微球表面接枝交联复合凝胶的制备及性能

为改善高分子微球复合凝胶响应速率慢及韧性差的缺陷,采用非交联温敏型疏水单体组装的高分子微球作为交联剂,在不外加交联剂的条件下制备微球表面接枝交联聚丙烯酰胺复合凝胶.由于微球内部无化学交联结构,因此可通过自身可逆性结构及形态改变对复合凝胶机械性能和刺激响应特性进行调控.复合凝胶具有良好的韧性,断裂伸长率和断裂强度分别可达2400%和80 k Pa,且凝胶机械强度可通过温度进行调控.由于温敏型微球交联点的存在,采用非敏感型聚丙烯酰胺为基质的复合凝胶对温度具有良好的响应性,其响应速率较传统聚N-异丙基丙烯酰胺有机凝胶提升5~10倍.     

聚(3-丙烯酰胺基苯硼酸-N,N-二甲基丙烯酰胺-丙烯酰胺)凝胶的合成和糖敏感性能

用自由基引发3-丙烯酰胺基苯硼酸(AAPBA)、N,N-二甲基丙烯酰胺(DMAA)和丙烯酰胺(AAm)共聚交联制得新型三嵌段水凝胶P(AAPBA-co-DMAA-co-AAm), 与传统的两嵌段聚合物相比, 该凝胶具有良好的糖敏感特性, 在质量浓度200 mg/dL以上有较高的糖响应特性, 这一数值接近糖尿病病人的血糖阈值, 其溶胀度达10倍以上, 同时糖响应时间缩短到2~3 h. 振荡实验结果表明, 所得凝胶对糖呈现出良好的刺激-响应特性.     

无外相的葡聚糖凝胶的合成

本文研究了无外相的葡聚糖凝胶的合成方法以及有关的催化剂用量,糖液浓度,反应时间,反应温度,交联剂用量和不同分子量的葡聚糖与合成凝胶的性能关系,并确定了最佳反应条件,从而制得了性能类似国外同类产品Sephadex的凝胶。     

智能纳米水凝胶的刺激响应性研究进展

智能纳米水凝胶在药物输送与可控释放、医学诊断、生物传感器、微反应器、催化剂载体等方面有良好的应用前景。结合本课题组近年来的研究成果,分别介绍了具有温度刺激响应性、pH刺激响应性、光刺激响应性、磁场刺激响应性、分子识别刺激响应性和多重刺激响应性智能纳米水凝胶的研究进展。另外,对这几种智能纳米水凝胶目前存在的问题和今后的发展方向提出了一些粗浅的看法。     

微凝胶增强两性复合水凝胶的制备与性能

将核壳微凝胶包埋在两性基质中,制备了复合水凝胶(CAH)。 研究发现,利用微凝胶与聚合物链之间的物理缠结作用,可以使复合凝胶具有致密的网络结构,力学性能显著提高;复合凝胶对pH和离子强度敏感,呈现出典型的两性聚电解质凝胶的溶胀行为。 同时微凝胶的存在和特殊的复合结构,可赋予CAH两性凝胶基质所不具有的响应性,并实现在高温下快速响应。     

粘土对N-异丙基丙烯酰胺和丙烯酸叔丁酯共聚形成微凝胶的影响

以无机粘土(锂蒙脱石)作为物理交联剂,在不加任何乳化剂的条件下,通过无皂乳液聚合制备了一系列粒径在250nm左右且具有温敏性的N-异丙基丙烯酰胺(NIPAM)和丙烯酸叔丁酯(tBA)共聚微凝胶,并通过傅立叶变换红外光谱、扫描电镜、准静态光散射、X射线衍射仪和差示扫描量热法对所合成微凝胶的化学结构、表面形态和温度敏感性进行了表征.研究表明,粘土起到交联剂的作用;tBA的引入可以调节微凝胶的体积相转变温度;所制得的粘土交联微凝胶具有较好的粒径分布且粒径在140nm至350nm之间.     

Tuning smart microgel swelling and responsive behavior through strong and weak polyelectrolyte pair assembly

The layer-by-layer (LbL) assembly of polyelectrolyte pairs on temperature and pH-sensitive cross-linked poly(N-isopropylacrylamide)-co-(methacrylic acid), poly(NIPAAm-co-MAA), microgels enabled a fine-tuning of the gel swelling and responsive behavior according to the mobility of the assembled polyelectrolyte (PE) pair and the composition of the outermost layer. Microbeads with well-defined morphology were initially prepared by synthesis in supercritical carbon dioxide. Upon LbL assembly of polyelectrolytes, interactions between the multilayers and the soft porous microgel led to differences in swelling and thermoresponsive behavior. For the weak PE pairs, namely poly(L-lysine)/poly(L-glutamic acid) and poly(allylamine hydrochloride)/poly(acrylic acid), polycation-terminated microgels were less swollen and more thermoresponsive than native microgel, whereas polyanion-terminated microgels were more swollen and not significantly responsive to temperature, in a quasi-reversible process with consecutive PE assembly. For the strong PE pair, poly(diallyldimethylammonium chloride)/poly(sodium styrene sulfonate), the differences among polycation and polyanion-terminated microgels are not sustained after the first PE bilayer due to extensive ionic cross-linking between the polyelectrolytes. The tendencies across the explored systems became less noteworthy in solutions with larger ionic strength due to overall charge shielding of the polyelectrolytes and microgel. ATR FT-IR studies correlated the swelling and responsive behavior after LbL assembly on the microgels with the extent of H-bonding and alternating charge distribution within the gel. Thus, the proposed LbL strategy may be a simple and flexible way to engineer smart microgels in terms of size, surface chemistry, overall charge and permeability.     

Synthesis and characterization of degradable p(HEMA) microgels: use of acid-labile crosslinkers

New divinyl-functionalized acetal-based crosslinkers were synthesized as building elements to form acid-labile microgel particles for controlled-release applications. The synthesized crosslinkers underwent hydrolysis at slightly acidic pHs in less than 1 h while they were stable at neutral pHs for longer times. HEMA was copolymerized with the crosslinkers via an inverse emulsion polymerization technique using a redox initiator system at room temperature to form crosslinked, colloidal p(HEMA) microgels. Microgels in diameters ranging from 150 to 475 nm with narrow distribution could be produced. The crosslinking density and the diameter of the microgels were found to be controlled by monomer/crosslinker feed ratio. The microgels demonstrated a pH-dependent cleavage behavior that mimicked the pH-dependent hydrolysis profile of the acid-labile crosslinkers. Model biomacromolecules, i.e., Rhodamine B-labeled dextran and BSA were efficiently loaded into the microgels. The release of the biomolecules from p(HEMA) microgels was also found to be controllable by the pH of the environment similar to the particle degradation. The protein released from the microgels was observed to retain its structural stability.     

Dual stimuli‐responsive microgels based on photolabile crosslinker: Temperature sensitivity and light‐induced degradation

The synthesis and characterization of a new photocleavable crosslinker is presented here. Dual stimuli‐responsive P(VCL‐co‐NHMA) microgels were prepared by precipitation polymerization of vinylcaprolactam (VCL) with N‐hydroxymethyl acrylamide (NHMA) and the new crosslinker. The microgels had distinct temperature sensitivity as observed in the case of PVCL‐based particles and their volume phase transition temperature (VPTT) shifted to higher temperature with increasing NHMA content. Photolytic degradation experiments were investigated by irradiation with UV light, which led to microgel disintegration caused by cleavage of the photolabile crosslinking points. The degradation behavior of the microgels was conducted with respect to degradation rates by means of the relative turbidity changes. Hence, the microgels could totally degrade into short linear polymers by UV light, thus representing a great potential as new light and temperature dual responsive nanoscale materials. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 1676–1685     

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.     

Designed glucose-responsive microgels with selective shrinking behavior

We report on the synthesis of various glucose-responsive microgels based on N-alkylacrylamide derivatives and phenylboronic acid (PBA) as a glucose sensing moiety. Depending on their chemical composition, the microgels exhibit opposite behaviors in response to glucose concentration increase: they can either swell or shrink, using two different mechanisms for glucose recognition. Both behaviors may be suitable for glucose sensing and insulin delivery. When glucose binds a single boronate receptor, the microgel swells as glucose concentration increases. This mechanism can be used to deliver a drug by diffusion through the network. In other cases, glucose binds specifically to two boronates, which creates additional cross-links within the network and provokes shrinkage. Such systems are promising for the development of sensors with improved selectivity and also as potential "intelligent" valves in microfabricated delivery systems. By a rational choice of the constituting units of the network structure, we show how to favor one or the other type of response to glucose variation. Therefore, glucose-swelling microgels operating under physiological conditions have been obtained by copolymerization with an appropriate choice of alkylacrylamide monomer and boronate derivative. At a pH above the pK(a) of the boronic acid derivative, the same structures shrink in response to glucose concentration. The nature of the cross-linker is a key parameter to enable this dual behavior. In other microgels, an amine group is introduced in the vicinity of the boronic acid, which lowers its pK(a) and favors microgel contraction at physiological pH. This work has allowed us to give some general rules to control the swelling/shrinking behavior of glucose-responsive microgels.     

The synthesis and responsive properties of novel glucose-responsive microgels

A novel routine for preparing of glucose-responsive microgels was developed. Following the routine of copolymerizing two functional monomers, a series of microgels with phenylboronic acid dispersed inside were prepared. The thermo-behavior of the microgel was tested, which revealed the retaining property of the thermo-responsive monomer after polymerization. In addition, the glucose-responsive behavior under different temperatures and pH values were also researched. It was demonstrated that the novel microgel was able to response to glucose. Furthermore, it was found that the swelling behavior of the microgel caused by glucose was enhanced, which benefited the drug release of the system.     

Inducing pH responsiveness via ultralow thiol content in polyacrylamide (micro)gels with labile crosslinks

Here we present the synthesis and characterization of pH responsive polyacrylamide microgels, synthesized via free radical polymerization of acrylamide and bis (acryloylcystamine) (BAC). The gels were made with ultralow amounts of thiol functional groups incorporated into the polymer. The resulting gel monoliths were mechanically chopped into microgel particles with size distributions ranging from 80 to 200 mum. The gels exhibit an interesting reversible pH-dependent rheological behavior which led to gelling of the colloidal suspension when the pH was increased, and a low-viscosity suspension was obtained when the pH was taken back to the original value. The viscosity of the colloidal system containing MBA crosslinked microgels remained insensitive to pH. This observation motivated further analysis; viscosity measurements of the highly viscous (gel-like) state of the BAC crosslinked microgel colloidal suspension were carried out to further understand the rheological behavior of the colloidal system. Electrophoretic mobility measurements as function of pH of the BAC and MBA crosslinked colloidal polyacrylamide microgel suspensions were performed. The swelling behavior of the microgels for both colloidal systems was also determined as function of pH using static light scattering. This swelling behavior was used to rationalize the observed rheological behavior. The work presented here demonstrates that free thiol groups present within a polymer gel matrix confer pH responsive behavior to the gel in solution. The viscosity of a BAC crosslinked microgel suspension was also measured under reducing conditions. The viscosity of the microgel suspension reduced with time, due to the breakage of the disulfide bonds in the crosslinkers.     

The Compressibility of pH‐Sensitive Microgels at the Oil–Water Interface: Higher Charge Leads to Less Repulsion

pH‐responsive microgels are unique stabilizers for stimuli‐sensitive emulsions that can be broken on demand by changing the pH value. However, recent experiments have indicated that electrostatic interactions play a different role to that in conventional Pickering emulsions. The influence of charges on the interactions between microgels at the oil–water interface is now described. Compression isotherms of microgels with different charge density and architecture were determined in a Langmuir trough, and counter‐intuitive results were obtained: Charged microgels can be compressed more easily than uncharged microgels. The compressibility of microgels is thus not determined by direct Coulomb repulsion. Instead, the different swelling of the microgels in the charged and the uncharged states is proposed to be the key parameter.     

Nanofibrillar Stimulus‐Responsive Cholesteric Microgels with Catalytic Properties

We report composite stimulus‐responsive cholesteric catalytically active microgels derived from filamentous supramolecular building blocks: cellulose nanocrystals (CNCs). The variation in the microgel dimensions and pitch in response to the change in ambient conditions was governed by the polymer component. The cholesteric morphology of the microgels resulted from the self‐organization of CNCs in spherical confinement. The microgels exhibited excellent structural integrity and functioned as microreactors in catalytic hydrolysis reactions and in the synthesis of metal nanoparticles. Because of these collective properties, the reported microgels show much promise for application in the design of functional responsive materials.