化学交联葡萄糖基取代聚膦腈水凝胶制备和胰岛素释放研究

在合成了葡萄糖基和甲氧乙氧基共取代聚膦腈的基础上,进一步通过向聚膦腈主链引入一定量带自由氨基的取代基,与戊二醛反应交联后,获得了具有化学交联点的聚膦腈水凝胶.该水凝胶与伴刀豆球蛋白(Con A)结合后,水凝胶的溶涨平衡性能表现出对葡萄糖浓度的依赖性.将负载有胰岛素的聚膦腈水凝胶交替置于含不同葡萄糖浓度(4 mg/mL和1 mg/mL)的介质中,可检测到在高浓度葡萄糖环境下,胰岛素的释放明显加快,而当葡萄糖的浓度降低后,在一段时间内几乎检测不到胰岛素的释放,但随着浸泡时间的延长,仍会逐渐出现胰岛素从凝胶缓慢扩散释放的现象.以上研究表明,化学交联的葡萄糖基取代聚膦腈水凝胶可用于对胰岛素的葡萄糖响应释放.     

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.     

Glucose-triggered release from liposomes incorporating poly(<Emphasis Type="Italic">N</Emphasis>-isopropylacrylamide-co-methacrylic acid-co-octadecylacrylate) and glucose oxidase

In order to design liposomes which release their contents in a glucose-sensitive manner, the surfaces of egg phosphatidylcholine (egg PC) liposomes or dioleoylphosphatidylethanolamine (DOPE) liposomes were modified with the copolymer of N-isopropylacrylamide/methacrylic acid/octadecylacrylate and hydrophobically modified glucose oxidase (EC 1.1.3.4.). Whichever the liposomes were prepared with egg PC or DOPE, an extensive release of calcein was observed at acidic conditions. And DOPE liposomes were more pH sensitive than egg PC liposomes in terms of the release. In glucose-dependent calcein release experiment, there was no release for 180 min when the suspension of liposome was free of glucose. When the glucose concentration was 50 mg/dl, no appreciable amount of calcein was released for the first 50 min, but a significant release was observed for the last 130 min. At glucose concentration of 200 mg/dl, calcein release became more extensive and the releases for 180 min from egg PC and DOPE liposome were 84% and 98%, respectively.     

苯硼酸类糖敏感微凝胶制备及其糖敏感性研究

制备了以葡聚糖作为交联剂的氨基苯硼酸类糖敏感微凝胶,用1H-NMR和FT-IR表征了其结构。利用微凝胶的不同条件下的粒径变化,深入研究了该类凝胶对糖浓度的刺激响应行为。结果表明,葡聚糖的引入使微凝胶在生理条件下具有更加优秀的依糖刺激响应行为。     

葡萄糖敏感型水凝胶最新研究进展

糖尿病是由于胰岛素分泌不足引起的一种新陈代谢疾病,对糖尿病的有效控制在于不间断的测定血糖浓度并适时的释放胰岛素.因此,能够对环境葡萄糖浓度变化做出应答的功能型高分子材料葡萄糖敏感水凝胶,在生物化学和生物医学领域引起了极大的关注.本文综述了近几年国内外葡萄糖敏感型水凝胶的研究现状,重点介绍了应用于胰岛素释放体系和生物传感器领域的载有葡萄糖氧化酶、伴刀豆球蛋白和苯硼酸基团等葡萄糖敏感型水凝胶的作用机理和最新研究进展,展望了今后的研究方向.     

Glucose oxidase-incorporated hydrogel thin film for fast optical glucose detecting under physiological conditions

Hydrogel biosensors usually suffer from a slow response, which severely hinders their practical applications. Here a new optical glucose biosensor was designed, using glucose-sensitive hydrogel films as both glucose-sensing material and Fabry-Perot cavity. The film was fabricated by layer-by-layer assembly from partially oxidized dextran (PO-Dex), chitosan, and glucose oxidase (GOD). The film responds to glucose because the incorporated GOD converts glucose to gluconic acid, and thus lowers the local pH in the film, and, in turn, triggers the pH-sensitive film to swell. The glucose-induced swelling causes a shift of Fabry?Perot fringes on the reflection spectra of the film, from which the glucose concentration can be reported. The new sensor works well under physiological conditions. Potential interferents, such as diols for phenylboronic acid-based sensors and electroactive compounds for electrochemical sensors, do not influence the new sensor. The sensor can respond reversibly over a wide range of glucose concentration. Particularly, it responds linearly within the clinically relevant glucose range (0–20 mM). More importantly, because the film is very thin, the new sensor can respond quickly, making it potential for real-time, continuous glucose monitoring.     

A chemo-electro-mechanical model for simulation of responsive deformation of glucose-sensitive hydrogels with the effect of enzyme catalysis

A multi-effect-coupling glucose-stimulus (MECglu) model is developed and solved numerically for the swelling behavior of soft smart hydrogels responding to changes in the environmental glucose concentration. The model considers the effect of the glucose oxidation reaction catalyzed by enzymes including glucose oxidase and catalase. It is composed of the Nernst-Planck equation for the mobile species in the solvent, the Poisson equation for the electric potential, and a nonlinear mechanical equation for the large deformations of the hydrogel that arise due to the conversion of chemical energy to mechanical. Based on the theory of the chemo-electro-mechanical-coupled fields, the formulation of the fixed charge groups bound onto the cross-linked polymer network is associated with the change of the ambient solution pH. The MECglu model is validated by comparison between the steady-state computation and experimental equilibrium swelling curves, and good agreement is obtained. A parameter study is then conducted by steady-state simulations to ascertain the impact of various solvent parameters on the responsive swelling behavior of the hydrogel. One key parameter is the glucose concentration, which is varied within the range of practical physiological glucose concentrations from 0 to 16.5 mM (300 mg/ml) to support the design and optimization of an insulin delivery system based on a glucose-sensitive hydrogel with immobilized glucose oxidase and catalase. The influence of oxygen and glucose concentrations in the solvent is then further studied for the distributive profiles of reacting and diffusive species concentrations, the electric potential, the displacement, as well as the swelling ratio of the glucose-sensitive hydrogel.     

苯硼酸类糖敏感材料的研究进展

糖尿病是由于胰腺分泌的胰岛素不足而引起的一种新陈代谢疾病。不间断地测定血糖浓度并依糖释放胰岛素是控制糖尿病的有效方法。因此,具有胰腺的反馈和平衡功能,能识别糖而产生刺激响应的智能系统,在糖尿病的控制和治疗方面有广泛的应用前景。糖作为生物体中的能源物质,与蛋白质、核酸并称生命体的三大组成单元,在生命活动中起着不可替代的作用。由于糖含有多个羟基,而苯硼酸可以与二醇、多醇羟基相互作用,故苯硼酸常被用于识别和感知糖,当荧光体与苯硼酸基团相连接时即可构建识别糖的荧光传感器。本文综述了近几年国内外关于含苯硼酸基团的糖敏感材料在生物医药领域的研究现状,重点介绍了苯硼酸类糖敏感药物缓控释智能材料和糖分子识别荧光探针的研究进展,展望了今后的研究方向。     

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...