pH敏感性P(AA-g-MPEGMac)水凝胶的制备及其性能研究

通过丙烯酰氯与聚乙二醇单甲醚(MPEG)酰化反应得到聚乙二醇单甲醚甲基丙烯酸酯(MPEGMac),将其与丙烯酸共聚得到MPEG侧链接枝并交联聚丙烯酸的pH敏感水凝胶P(AA-g-MPEGMac),研究了pH、单体配比对凝胶溶胀性能、溶胀动力学和退溶胀动力学的影响。初步探讨了模拟胃液(pH 1.4)和肠液(pH 7.4)中水凝胶对茶碱的控释情况。结果表明,凝胶具备良好的pH敏感性和快速的退溶胀速率等特征;溶胀初期水的扩散趋于non-Fickian模式,水凝胶的溶胀行为满足Schott二级动力学方程;载药凝胶在模拟肠液中对药物的累计释放率明显大于胃液中的累计释放率。     

Na~+的引入对P(Am-co-SMA)水凝胶溶胀性及pH敏感性的影响

采用自由基聚合法分别制备丙烯酰胺(Am)、甲基丙烯酸(MA)含量不同的聚(Am-co-MA)[P(Amco-MA)]水凝胶,以及引入Na~+制备聚(Am-co-甲基丙烯酸钠)[P(Am-co-SMA)]水凝胶,并对这些水凝胶的溶胀性及pH敏感性进行研究。结果表明:P(Am-co-MA)水凝胶的溶胀性和pH敏感性较聚丙烯酰胺水凝胶高,而P(Am-co-SMA)水凝胶则表现出了更高的溶胀性和pH敏感性,且网孔出现塌陷结构。水凝胶的这些特殊性能使其有望应用于药物的缓控释放领域。     

聚甲基丙烯酸/丙烯酰胺pH敏感凝胶的合成与溶胀行为研究

以单体丙烯酰胺(AM)、甲基丙烯酸(MAA),交联剂N-N'亚甲基双丙酰胺(BIS)为原料,通过自由基共聚合成了聚甲基丙烯酸/丙烯酰胺[P(MAA-co-AM)]水凝胶.研究了干凝胶在不同pH溶液中的溶胀动力学,结果表明不同AM、MAA单体配比的凝胶溶胀性具有很大差异,其溶胀率都随着溶液的pH增加而增大,在pH=12和pH=2溶液反复变换时显示可逆溶胀-退溶胀和快速响应特性,溶胀-退溶胀过程中搅拌作用对凝胶响应速率有显著影响.吸水平衡P(MAA-co-AM)水凝胶在酸性及碱性条件下均出现收缩,在pH=2下10 min之内凝胶收缩90%以上,随着pH增大逐渐减慢.通过不同浓度的NaCl与CaCl2溶液研究了溶液离子强度以及反离子的电荷数对凝胶溶胀性影响,在NaCl溶液和水中,呈现反复溶胀-退溶胀响应特性.     

聚甲基丙烯酸N,N-二甲基氨基乙酯水凝胶敏感性研究

采用热化学聚合法制备了聚甲基丙烯酸N,N-二甲基氨基乙酯(PDMAEMA)水凝胶,对其溶胀性能进行了研究,考察了温度、pH和离子强度对其溶胀行为的影响.结果表明,PDMAEMA水凝胶具有温度敏感性,其低临界相变温度在50℃左右;水凝胶具有pH敏感性,其溶胀率在pH=8附近有一突变的下降过程;具有离子强度敏感性,溶胀率随离子强度的增加呈线性下降的趋势.     

β-环糊精/海藻酸钠水凝胶的制备及性能研究

将海藻酸钠(SA)和β-环糊精(β-CD)共混制备了复合水凝胶,并讨论了交联剂浓度、原料配比对水凝胶溶胀性能的影响。结果表明,当两者的共混比例为1∶2、w(交联剂)为6%、交联时间为1h时,水凝胶的溶胀性能较好。水凝胶在pH=1.2时的溶胀率仅为1.2,而在pH=7.4时的溶胀率达到14.2,具有良好的pH敏感性。以牛血清蛋白(BSA)为模型药物,研究了β-CD/SA水凝胶作为药物载体对BSA的负载及释放性能,结果表明:在模拟胃液中的累计释放量较小(21.5%),且释放速率较慢;在模拟肠液中的累计释放量为70.2%,具有良好的pH敏感控制释放性能。     

AM与HEMA共聚制备水凝胶接触镜材料及其溶胀性能

采用丙烯酰胺(AM)与甲基丙烯酸β-羟乙酯(HEMA)进行本体共聚制备水凝胶接触镜材料,研究了水凝胶的溶胀性能及其温度和pH值敏感性。结果表明,引发剂过氧化苯甲酰(BPO)用量为反应单体总质量的0.3%、反应温度80℃,产物溶胀之后为无色透明的玻璃状水凝胶;共聚物水凝胶具有较好的pH值敏感性,水凝胶在酸性溶液中溶胀,在碱性溶液中收缩:含有AM的水凝胶,其pH值敏感性较大:随AM的含量增大,共聚物水凝胶的溶胀速度和饱和含水量增大,随温度升高,水凝胶的饱和含水量下降,共聚物水凝胶中AM的含量对其温度敏感性无显著影响:SEM照片显示,AM与HEMA共聚物存在均匀的纤维状结构,并且共聚物中AM的含量越大,这种纤维状结构越大、越明显。     

快速响应性智能水凝胶的制备及药物缓释模拟

采用紫外光照引发聚合法,以85%乙醇溶液为反应介质,不同分子量的聚乙二醇(PEG)作为致孔剂,成功合成了具有温度和pH双重敏感性的聚(N-异丙基丙烯酰胺-co-甲基丙烯酸)[P(NIPAM-co-MAA)]智能型水凝胶。利用红外光谱仪(FT-IR)、扫描电镜(SEM)测定退/溶胀率,并对凝胶进行表征,分析原料配比对凝胶性能的影响,并以乙酰水杨酸为模型药物研究了药物释放性能。结果表明,具有大孔结构的双重敏感性水凝胶能够在特定温度和pH环境下,快速平稳地释放药物,并且随着PEG分子量的增大,水凝胶的载药率和药物释放速率均得到提高。     

印迹水凝胶作为氟尿嘧啶载体的药物缓释性能

以氟尿嘧啶为模板药物,以甲基丙烯酸羟乙酯为骨架单体,以甲基丙烯酸为功能单体,乙二醇二甲基丙烯酸酯为交联剂,偶氮二异丁腈为引发剂合成印迹水凝胶,并通过扫描电镜、红外光谱及差示热量扫描等测试手段对凝胶进行了表征,结果表明：制备的印迹水凝胶表面无孔、光滑,氟尿嘧啶与其中的单体通过氢键结合成了复合物,同时经处理后凝胶中已不再残留未反应的单体。印迹水凝胶的吸水溶胀性能实验结果显示其吸水溶胀性能随制备中模板药物的含量的增加而增强,同时同一凝胶的溶胀速度与溶胀率随体系pH值的升高而增强。在氟尿嘧啶溶液中测定水凝胶的药物负载量,结果显示：印迹水凝胶的药物负载能力明显强于非印迹水凝胶,同时印迹水凝胶（8∶1）对药物的负载能力强于印迹水凝胶（4∶1）,药物负载量高达0.0914 mg/g。在模拟体液中测试水凝胶对药物的释放效果结果显示：印迹水凝胶对药物的缓释作用明显优于非印迹水凝胶,并且印迹水凝胶（8∶1）对药物的缓释效果优于印迹水凝胶（4∶1）,对药物的释放平缓,同时,释放体系pH值的升高不利于印迹水凝胶的药物缓释效果。     

pH敏感型半纤维素水凝胶的制备及释药性能研究

利用自由基聚合方法制备了丙烯酸和丙烯酰胺共聚接枝半纤维素水凝胶,研究了水凝胶在不同pH(1.5、7.4、10)缓冲液中的溶胀动力学,并以阿司匹林作为模型药物,研究了其在模拟胃肠液(pH=1.5、7.4)中的释放性能。结果显示,制备的半纤维素水凝胶对阿司匹林具有明显的缓释效果,有望实现药物的控制释放。     

pH-温度双重敏感性水凝胶的制备及溶胀性能研究

制备具有pH及温度双重敏感性水凝胶。通过自由基聚合反应制备出NIPAM-co-PMAA水凝胶材料。考察不同单体甲基丙烯酸(MAA)和N-异丙基丙烯酰胺(NIPA)配比对pH和温度的响应能力,探究其溶胀性能。结果表明,不同配比的水凝胶具有双重敏感性。NIPA含量不同时,对于LSCT温度有影响,MAA含量不同时,在酸性条件下溶胀率较大。结论,NIPAM-co-PMAA水凝胶有望成为药物载体。     

Preparation and application in drug controlled delivery of pH‐sensitive P(CE‐co‐DMAEMA‐co‐MEG) hydrogel

A pH‐sensitive hydrogel [P(CE‐co‐DMAEMA‐co‐MEG)] was synthesized by the free‐radical crosslinking polymerization of N,N‐dimethylaminoethyl methacrylate (DMAEMA), poly(ethylene glycol) methyl ether methacrylate(MPEG‐Mac) and methoxyl poly(ethylene glycol)‐poly(caprolactone)‐methacryloyl methchloride (PCE‐Mac). The effects of pH and monomer content on swelling property, swelling and deswelling kinetics of the hydrogels were examined and hydrogel microstructures were investigated by SEM. Sodium salicylate was chosen as a model drug and the controlled‐release properties of hydrogels were pilot studied. The results indicated that the swelling ratios of the gels in stimulated gastric fluids (SGF, pH = 1.4) were higher than those in stimulated intestinal fluids (SIF, pH = 7.4), and followed a non‐Fickian and a Fickian diffusion mechanism, respectively. In vitro release studies showed that its release rate depends on different swelling of the network as a function of the environmental pH and DMAEMA content. SEM micrographs showed homogenous pore structure of the hydrogel with open pores at pH 1.4. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40737.     

温度和pH双重敏感性水凝胶的制备及表征

在5种不同温度下聚合交联,制备了一系列温度和pH双重敏感性聚(N-异丙基丙烯酰胺-co-衣康酸)水凝胶。实验发现,15、25℃得到的凝胶是透明的,45、55℃得到的凝胶是白色不透明的,而在相转变温度附近(35℃)得到的凝胶则是半透明的。FTIR测定表明,它们具有相似的化学组成和结构。SEM观察证实,它们具有不同的表面形态。测定了不同温度和pH下达到平衡时水凝胶的溶胀比,考察了水凝胶在水和强酸性溶液中的去溶胀动力学。结果表明,与15℃或25℃制备的水凝胶相比,45℃和55℃制备的水凝胶的性能有显著提高:(1)溶胀比大为增加。15℃或25℃制备的水凝胶在25℃时溶胀比分别为65.3和68.1,而45℃和55℃制备的水凝胶此时溶胀比分别高达105.7和110.1;(2)45℃和55℃制备的水凝胶在极端环境下对温度的变化仍具有较快的响应速率。例如在温度为60℃,pH=1.67的强酸条件下,45℃和55℃制备的水凝胶在60 min内皆可失去95%的水,而15℃或25℃制备的水凝胶在120 min内只能失去42%左右的水。     

Synthesis,Characterization, and drug release study of acrylamide‐co‐itaconic acid based smart hydrogel

A new kind of pH and temperature responsive poly(acrylamide‐co‐itaconic acid) hydrogel was prepared by free radical polymerization using ammonium persulfate as initiator and different comonomer ratios. The hydrogels were characterized in terms of chemical composition, swelling‐deswelling behavior, morphology, crystallographic behavior, and drug release properties. All the hydrogels showed high swelling ability in aqueous solutions, the maximum being at pH 7. Swelling decreased on either side of pH 7 (i.e., both in acidic and alkaline region) and increased with increase in temperature. The hydrogel with 10 mol% itaconic acid (IA) absorbed maximum water among the copolymer gels. The cellular structures of the hydrogels were clearly revealed by microscopic analysis and SEM pictures. Swelling of the gels in water followed non‐Fickian type of diffusion principle. The hydrogel was proved to be a controlled release vehicle, for example in drug delivery by using its smart properties. The hydrogel with 10 mol% IA also absorbed maximum amount of drug (ascorbic acid) under study. Incorporation of drug in hydrogel matrix was established from XRD peak analysis. POLYM. ENG. SCI., 55:113–122, 2015. © 2014 Society of Plastics Engineers     

Synthesis and Characterization of Temperature-Sensitive Poly(N-isopropylacryamide) Hydrogel with Comonomer and Semi-IPN material

A series of temperature and pH sensitive hydrogels were synthesized using N-isopropylacrylamide (NIPAAm) as main monomer, sodium alginate (SA) as semi-IPN material, ethyl acrylate (EA) and acrylic acid (AA) as comonomer, and N-maleyl chitosan (N-MACH) as cross-linker. The temperature and pH sensitive behavior, swelling/deswelling kinetics of the hydrogels were investigated. And the mechanism of the phase transition was summed up. Sodium alginate/Poly(N-isopropylacryamide) semi-interpenetrating polymer network (SA/PNIPAAm semi-IPN) hydrogels exhibited a lower critical solution temperature (LCST) at about 32 °C with no significant deviation from the conventional PNIPAAm hydrogels. Poly(N-isopropylacryamide-co-ethyl acrylate) (P(NIPAAm-co-EA)) hydrogels exhibited LCST at 29–31°C, increasing the amount of EA in the hydrogel gradually decreased the LCST. Poly(N-isopropylacryamide-co-acrylic acid) [P(NIPAAm-co-AA)] hydrogels exhibited LCST at 34–39°C, with decreasing NIPAAm/AA from 96/4 to 92/8 and 90/10, the LCST increased from 34°C to 37°C and 39°C. In the swelling/deswelling kinetics, all the dried hydrogels exhibited fast swelling/deswelling behavior, which might be attributed to macroporous structures of the hydrogels.     

Synthesis and characterization of pH- and/or temperature-sensitive hydrogels

A series of pH-sensitive hydrogels that exhibit volume phase transition phenomena have been synthesized in aqueous solution and characterized with respect to their dynamic swelling behaviors. Positively charged hydrogels were prepared by copolymerizing varying ratios of N-isopropylacrylamide and NN′-dimethylaminopropylmethacrylamide. The hydrogels based on a temperature-sensitive hydrogel demonstrate a large change of equilibrium swelling in response to small variations of pH and/or temperature. These hydrogels exhibit different lower critical solution temperature (LCST) ranges depending on the environmental pH values. Below their LCST, they exhibit small and broad pH sensitivities normally observed in most hydrophilic polyelectrolyte gels, but above their LCST, they exhibit sharp pH dependent phase transition behaviors. The pH-dependent phase transition is strongly affected by temperature, while the temperature-dependent transition is, in turn, largely influenced by the pH. As the temperature is raised, the transitional degree of gel swelling change becomes sharper and larger, and the phase transition pH value shifts to a lower pH. It was also found that swelling is faster than deswelling for these cationic hydrogels, which suggests the existence of a water diffusion barrier during the deswelling. The swelling kinetics of initially dry and glassy gels were strongly dependent on both the pH value and temperature.     

Superabsorbent hydrogels from poly(aspartic acid) with salt-, temperature- and pH-responsiveness properties

Polyaspartic acid (PAsp) resin was synthesized by polysuccinimide (PSI), through chemical cross-linking using the cross-linking agent (diamine). The effects of reaction variables, such as PSI concentration and terminal pH on the water absorbent capacity have been studied. These phenomena were discussed according to structural parameters, which were confirmed by SEM. Water absorbencies were compared for the hydrogels at terminal pH 8 and 10. The water absorbent capacity enhanced with increasing terminal pH and decreasing PSI concentration. The swelling/deswelling kinetics of the super-absorbent hydrogels was investigated as well. It is found that the hydrogels showed ampholytic and reversible pH-responsiveness properties. The variational water absorbencies were attributed to swelling theory based on the hydrogel physical and chemical structure. The swelling was also extremely sensitive to the temperature, ionic strength and cationic kind. The reversible pH-responsiveness, salt- and temperature-sensitivity of the hydrogels make this intelligentized polymer had wider applications.     

Synthesis and characterization of pH- and thermoresponsive Poly(<Emphasis Type="Italic">N</Emphasis>-isopropylacrylamide-co-itaconic acid) hydrogels crosslinked with <Emphasis Type="Italic">N</Emphasis>-maleyl chitosan

Biodegradable cross-linker N-maleyl chitosan (N-MACH) was synthesized with chitosan (CS) and maleic anhydride (MA) by acylation. With N-MACH cross-linker, a series of cross-linked poly(N-isopropylacrylamide-co-itaconic acid) [P(NIPAAm-co-IA)] hydrogels were prepared, and their pH-and temperature-responsive behaviors, water contents, swelling/deswelling kinetics were investigated. By alternating the NIPAAm/IA weight ratios, hydrogels had the volume phase transition temperature (VPTT) changed from 33 to 38 °C, whereas cross-linking density did not affect the VPTT apparently. The water content of hydrogels was controlled by the monomer weight ratios of NIPAAm/IA, swelling media, and the cross-linking density. The results of the influence of pH value on the swelling behaviors showed that the minimum swelling ratios of the hydrogels appeared in neutral buffer solution, which was attributed to chemical composition of the hydrogels and the swelling media. In the swelling/deswelling kinetics, all the dried hydrogels exhibited fast swelling within 480 min and fast deswelling within 20 min, which was independent of the content of IA and cross-linker.     

Hydrogels for oral drug delivery of peptides: Synthesis and characterization

In this study hydrogels were synthesized by the copolymerization of acrylamide and itaconic acid in the presence of poly(N‐vinyl‐2‐pyrrolidone) in an aqueous medium. The incorporation of a small amount of itaconic acid resulted in the transition of the swelling behavior from Fickian to non‐Fickian. The hydrogels showed good response to the valency of the counterions and pH of the swelling media. The equilibrium water uptake increased with the pH of the external solution, thus attaining a maximum value at pH 7–8. The gels exhibited a number of deswelling–swelling cycles while maintaining mechanical strength and shape stability. The amount of itaconic acid present in the system affected the swelling behavior of the hydrogels in a rather unusual way. At pH 2.0 the equilibrium water uptake increased with the amount of acid monomer up to 15 mM, remained almost constant for a very small range of concentrations (i.e., up to 22 mM), and then finally decreased with the further increase of the acid content. However, a continuous increase was observed at the pH 7.0 of the swelling media. The hydrogels showed very poor temperature dependency and the activation energies for the samples with and without itaconic acid were 29.09 and 19.92 kJ mol^?1, respectively. Finally, the swelling and deswelling processes were explained on the basis of two different mechanisms that were followed by the gels. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 83: 1717–1729, 2002     

Heterogeneous and homogeneous structure dextran–poly(methacrylic acid) interpenetrating network hydrogels: synthesis and an application study

pH‐sensitive dextran–poly(methacrylic acid) (Dext–pMeAc) full interpenetrating network hydrogels (INHs) were prepared by simultaneous radical polymerization of methacrylic acid monomer (MeAc) and Dext polymer chains in the presence of N,N‐methylenebisacrylamide (MBA) as crosslinker in aqueous solution. These hydrogels were investigated as a drug carrier. The influence of MeAc and MBA contents in the network hydrogels on the swelling behaviour and mechanical strength of prepared Dext–pMeAc INHs was evaluated. Dext–pMeAc INHs were characterized by Fourier transform IR spectroscopy, and kinetic swelling measurements were carried out in deionized water and in simulated gastric fluids (pH 1.1 and pH 7.4). Dext–pMeAc/1‐1, Dext–pMeAc/3‐1 and Dext–pMeAc/5‐1 hydrogels with molar ratios of n_Dext/n_MeAc = 10 and n_MBA/n_Dext = 10, 30 and 50 respectively showed a core–shell structure when they swelled. This phenomenon was not observed in Dext–pMeAc/5‐2, Dext–pMeAc/5‐3 and Dext–pMeAc/5‐5 hydrogels containing a higher amount of Dext in the gels. The swelling data proved the formation of INHs with pH‐sensitive behaviour. A drug release study was performed using Rhodamine 6G fluorescent dye as a model hydrophilic bioactive molecule. The in vitro release rate of Rhodamine 6G from Dext–pMeAc/5‐3 hydrogel was dependent on the pH of the release medium. Copyright © 2012 Society of Chemical Industry     

Poly(N,N-dimethylaminoethyl methacrylate)/graphene oxide hybrid hydrogels: pH and temperature sensitivities and Cr(VI) adsorption

Different amounts of graphene oxide (GO) were incorporated to N,N-dimethylaminoethyl methacrylate (DMAEMA), fabricating a series of pH and temperature dual sensitive PDMAEMA/GO hybrid hydrogels by in situ polymerization. Their microscopic network structures as well as swelling properties and Cr(VI) adsorption were characterized. The equilibrium swelling ratios (ESR) of hydrogels increased significantly with 0.5 wt% GO feeding of DMAEMA amount, and then decreased with further GO loading increasing. All hydrogels showed obvious deswelling when pH value of swelling mediums increased from 5 to 10 gradually. At pH 7, hydrogels revealed slight ESR increment with temperature up to 50 °C, above which obvious deswelling occurred. In pH 8 buffer, 0.5 wt% of GO loading triggered lower critical solution temperature (LCST) to decrease by 3 °C, and 2–7 °C increment was observed when 1–6 wt% of GO was loaded, as compared with that of GO-free PDMAEMA hydrogel. Cr(VI) adsorption of hydrogels was also improved by the introduction of GO to some extent, and the maximum Cr(VI) adsorption of 180 mg/g was realized, indicating that the obtained PDMAEMA/GO hybrid hydrogels possess excellent adsorption performance.