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。     

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。     

温度及pH敏感性互穿网络水凝胶的制备研究

采用分步法制备了聚丙烯酸/N-异丙基丙烯酰胺互穿网络水凝胶,研究了互穿网络水凝胶的溶胀性能。结果表明,当水溶液的pH增大时,水凝胶的溶胀率显著增加。在一定的温度范围内,水凝胶的溶胀率随温度升高而减小。聚丙烯酸/N-异丙基丙烯酰胺互穿网络水凝胶表现出显著的温度及pH敏感双重特性。     

温度及pH敏感性聚乙烯醇/羧甲基壳聚糖水凝胶的制备与性能研究

以聚乙烯醇(PVA)和羧甲基壳聚糖(CMCh)为原料,采用60Co-γ射线辐照交联制备聚乙烯醇/羧甲基壳聚糖(PVA/CMCh)水凝胶;研究了PVA与CMCh的配比、温度、pH及离子强度等对PVA/CMCh水凝胶溶胀率的影响。结果表明适当配比的PVA/CMCh水凝胶具有一定的温度、pH及离子敏感性。该水凝胶在5~20°C时具有较高的溶胀率,温度在20°C以上溶胀率较低,并且有一定的可逆性;水凝胶在pH较低(pH<4.0)和较高(pH>6.0)时溶胀率均较大,而当pH为4.0~6.0时溶胀率较小,显示出一定的pH敏感性。     

温度及pH敏感生物水凝胶的研究

运用互穿网络技术,合成了具有温敏性的聚(N 异丙基丙烯酰胺)(PNIPAm)和生物大分子明胶(gelatin)的互穿网络聚合物(PNIPAm/Gelatinsemi IPN和PNIPAm/GelatinIPN)水凝胶,该水凝胶的最低临界溶液温度(LCST)与PNIPAm水凝胶的LCST基本相同,均为33℃左右,但在LCST以下的平衡溶胀率减小、相变区域略微变宽。在此基础上,通过N 异丙基丙烯酰胺(NIPAm)与丙烯酸(AAc)交联共聚,改变了水凝胶的LCST,在pH=4 0的缓冲溶液中,各水凝胶的溶胀行为基本一致,与AAc含量无关,LCST都为28℃左右;在pH>4 0的缓冲溶液中,LCST随AAc组分含量的增加而增加,但温敏性减小。同时,AAc的加入,使水凝胶具有pH敏感性,敏感点为pH=4 5左右。还考察了该水凝胶降解的特点:戊二醛(GA)交联后的明胶网络,保留了明胶的生物降解性,但互穿网络水凝胶在实验条件下几乎未被胃蛋白酶和胰蛋白酶降解,在pH=9 6的碱性条件下,水凝胶可发生化学降解。     

温度/pH敏感型壳聚糖水凝胶的制备及其性能

以天然可降解高分子壳聚糖为载体,选择温度敏感单体N-异丙基丙烯酰胺以及pH敏感单体2-丙烯酰胺基-2-甲基丙磺酸,以偶氮二异丁腈为引发剂,N,N-亚甲基双丙烯酰胺为交联剂,通过自由基接枝共聚反应制备壳聚糖水凝胶。通过红外(IR)、扫描电镜(SEM)对其结构及形貌进行了表征,并探讨了影响水凝胶溶胀率的因素。结果表明,当单体配比NIPAM∶AMPS为6∶4、引发剂用量为单体总质量4%、交联剂用量为单体总质量的4%、反应温度为45℃形成的水凝胶在水中溶胀率可达95%左右。该水凝胶具有一定的温度和pH敏感性,预计在药物控释、组织工程、抗凝血材料等领域拥有广阔的应用前景。     

温度和pH双重敏感性聚氨酯水凝胶的合成及性能研究

采用逐步聚合凝胶法完成对含有端烯基聚氨酯(UAA)预聚物与N-异丙基丙烯酰胺(NIPA)共聚,得到具有温度和pH双重敏感性的聚氨酯水凝胶。通过对该凝胶最大溶胀形貌观察,在不同温度及pH环境中对溶胀性能的探讨,发现该凝胶空间结构、溶胀性等方面适合作药物缓释。选用模拟药物茶碱,在模拟人体消化系统,即不同pH条件下对其缓释,7 h基本释放完,茶碱浓度相对稳定。因此,该材料在介入诊疗方面有极大的应用潜力,是一种有着巨大应用前景的生物医用材料。     

新型胶原基pH敏感水凝胶的制备及性能

在紫外光辐照下,以H2O2为引发剂,采用接枝共聚法制备胶原/聚乙烯吡咯烷酮/丙烯酰胺（Collagen/PVP/AM）pH敏感水凝胶。考察了原料配比和干燥方法对凝胶溶胀性能的影响,研究了其pH敏感性及pH溶胀-退胀特性。制备的水凝胶具有较快的溶胀速率,在5 min时的吸水率可达94％左右。所制备的水凝胶有明显的pH敏感性且pH溶胀-退胀的可逆性良好。傅里叶变换红外光谱法（FTIR）和示差扫描量热法（DSC）结果表明,在保持胶原三股螺旋结构的同时,材料间发生了化学交联,材料的热稳定性显著提高,从而扩大了材料的应用范围。     

温度、pH敏感性共聚物(MA-co-NIPMAM)水凝胶的制备及性能研究

以N,N′-亚甲基双丙烯酰胺(MBA)为交联剂,以甲基丙烯酸(MA)和N-异丙基甲基丙烯酰胺(NIPMAM)作为聚合单体合成具有温度及p H双重敏感性的水凝胶。研究了MBA的用量与水凝胶溶胀过程的影响。在25℃和55℃下分别研究水凝胶在酸性和碱性条件下的去溶胀动力学和再溶胀动力学过程。     

pH敏感性水凝胶的制备与作用原理

对pH敏感性水凝胶的合成方法和作用原理进行了综述。pH敏感性水凝胶的合成方法主要包括交联聚合、接枝共聚和互穿网络三种方式；pH敏感性水凝胶具有pH响应性的原因是聚合物网络中含有可离子化的酸性或碱性基团。     

Investigation of swelling and controlled-release behaviors of hydrophobically modified poly(methacrylic acid) hydrogels

Using hydrophobic acrylic acid-2-ethylhexyl ester (AAEHE) as a comonomer of methacrylic acid (MAA), a series of hydrophobically modified (HM) poly(methacrylic acid) (PMAA) (HMPMAA) hydrogels were prepared by UV solution copolymerization and studied as controlled-release matrices. The result indicates that swelling degree of the HMPMAA hydrogels can sensitively respond to change in pH. However, the presence of hydrophobic AAEHE segments influences swelling kinetics of PMAA hydrogel evidently. Using p-hydroxyanisole (PHAS) as a model molecule, controlled-release behaviors of the HMPMAA hydrogels were investigated. It is found that the presence of hydrophobic AAEHE segments can markedly slow down the release rate of PHAS from PMAA-based hydrogels regardless of pH 1.4 or 7.4.     

Synthesis and swelling properties of pH‐sensitive hydrogels based on chitosan and poly(methacrylic acid) semi‐interpenetrating polymer network

A novel semi‐interpenetrating polymer network (semi‐IPN) hydrogel composed of chitosan and poly(methacrylic acid) was synthesized using formaldehyde as a crosslinker. The amount of crosslinker was searched and optimized. The structure of the hydogel was investigated by Fourier transform infrared (FTIR) spectroscopy. The spectrum shows that a structure of polyelectrolyte complex exists in the hydrogel. The effects of pH, ionic strength, and inorganic salt on the swelling behaviors of the hydrogel were studied. The results indicate the hydrogel has excellent pH sensitivity in the range of pH 1.40 to 4.50, pH reversible response between pH 1.80 and 6.80, and ionic strength reversible response between ionic strength 0.2 and 2.0M. The results also show that the hydrogel has a bit higher swelling capacity in a mix solution of calcium chloride (CaCl₂) and hydrochloric acid (HCl) solution than in a mix solution of sodium chloride (NaCl) and HCl. These results were further confirmed through morphological change measured by scanning electron microscope (SEM). © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 1720–1726, 2005     

Molecular design of novel pH/temperature-sensitive hydrogels

A series of poly(β-amino ester)-poly(?-caprolactone)-poly(ethylene glycol)-poly(?-caprolactone)-poly(β-amino ester) pentablock copolymers (PAE-PCL-PEG-PCL-PAE) were designed and prepared to examine factors affecting sol-gel phase transition behavior. First, the composition of a series of PCL-PEG-PCL copolymers was controlled by changing the feed ratios of PCL/PEG and the molecular weight of PEG. Second, the composition of pentablock copolymers was varied using different PCL-PEG-PCL copolymers and several feed ratios of PAE monomers. The physicochemical properties of triblock and pentablock copolymers were characterized by ¹H NMR and gel permeation spectroscopy. The PAE-PCL-PEG-PCL-PAE copolymers in aqueous solution (20-30 wt%) underwent sol-gel transitions with changes in both pH change and temperature. With increasing molecular weight of PAE, the sol-gel transition zone became narrower because the hydrophobic character of the copolymers decreased. Also, with increases in PCL/PEG ratio and PEG molecular weight, changes in the hydrophobic/hydrophilic balance within copolymers resulted in alterations in sol-gel phase transitions.     

pH- and temperature-sensitive multiblock copolymer hydrogels composed of poly(ethylene glycol) and poly(amino urethane)

A series of novel pH- and temperature-responsive multiblock copolymers (poly(PEG/HEP urethane)) consisting of poly(ethylene glycol) (PEG) and poly(amino urethane) (PAU) were synthesized, and their physicochemical properties were studied. The amphiphilic block copolymers were synthesized from PEG, 1,4-bis(hydroxyethyl) piperazine (HEP) and 1,6-diisocyanato hexamethylene (HDI) in the presence of dibutyltin dilaurate as a catalyst. The resulting polymers were examined by FT-IR, ¹H and ¹³C NMR spectroscopies and gel permeation chromatography (GPC). The solution properties of the copolymers were studied by turbidity measurement and fluorescence spectroscopy. The copolymers showed a pH-dependent soluble-insoluble transition in diluted aqueous solutions. The concentrated polymer solutions exhibited a thermo-induced sol-gel-sol phase transition at pH 6.8-7.4. The gel window covers the physiological conditions. After a subcutaneous injection of the multiblock copolymer solution into mice, a transparent and soft gel was formed immediately. The in vitro release of a model anticancer drug, chlorambucil, persisted over 2 weeks under physiological conditions.     

Amino acid functionalized pH- and temperature-sensitive biodegradable injectable hydrogels: synthesis,physicochemical characterization and in vivo degradation kinetics

Abstract

In recent years, injectable hydrogels that undergo sol-to-gel phase transition in response to the physiological pH- and temperature have attracted increasing attention in therapeutics delivery. In this study, we developed a biodegradable pH- and temperature-sensitive pentablock copolymers by chemical conjugation of L-cysteine oligomer to the backbone of poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide) (PCLA-PEG-PCLA) copolymers. A series of pentablock copolymers with various chain lengths were prepared by tuning the reaction time and temperature. These copolymers were freely soluble in water at high pH and low temperature; whereas, they could form a stable gel at the physiological condition (pH 7.4, 37?°C). An in vivo injectable study in the back of Sprague-Dawley (SD) rats indicated that the copolymer could form an in situ gel. In addition, an in vivo biodegradation study of the hydrogels showed controlled degradation of the gel matrix without inflammation at the injection site. Overall, our results show that biodegradable pH- and temperature-responsive hydrogel prepared in this study found to be bioresorbable and could be used as a controlled therapeutics delivery vehicle.     

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.     

Gamma radiation synthesis and swelling properties of hydrogels based on poly(ethylene glycol)/methacrylic acid (MAc) mixtures

In this work, gamma radiation was used to prepare hydrophilic hydrogels based on different mass ratios of poly(ethylene glycol) (PEG) and methacrylic acid (MAc) monomer. The thermal stability of hydrogels was characterized thermogravimetric analysis (TGA). The effect of temperature and pH, as external environments, on the equilibrium swelling of PEG/MAc hydrogels was also studied. The results showed that the gel fraction of PEG/MAc hydrogels is lower than that of PMAc hydrogel, in which the gel fraction of PMAc hydrogel was decreased greatly with increasing the mass ratio of PEG polymer in the initial solutions. The results showed that PEG/MAc hydrogels reached the equilibrium swelling state in water after 6 hours. It was found that the equilibrium swelling of PEG/MAc hydrogels displayed a transition change within the temperature range 30–40°C. This change in equilibrium swelling was illustrated by differential scanning calorimetry (DSC). However, it was observed that the equilibrium swelling of PEG/MAc hydrogels increases progressively with increasing the pH value from 4 up to 8. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Study of dual responsive poly[(maleilated dextran)‐graft‐(N‐isopropylacrylamide)] hydrogel nanoparticles: preparation,characterization and biological evaluation

BACKGROUND: Much interest has recently been shown in fundamental studies and technological developments of polymeric nanoparticles. Novel dual temperature‐ and pH‐sensitive stabilized nanoparticles composed of maleilated dextran (Dex‐MA) and N‐isopropylacrylamide (NIPAAm) were prepared and investigated to be used for the controlled release of 10‐hydroxycamptothecin. RESULTS: The resultant nanoparticles showed spherical geometry, with diameters ranging from 60 to 300 nm, the variation achieved by adjusting the composition ratio or the amounts of surfactant. The size of the nanoparticles increased and the zeta potential reversed with an increase of pH. Also, the lower critical solution temperature (LCST) decreased at pH = 3.0, but increased at pH = 6.0, which suggests that the LCST is dependent on pH. Drug release results obtained showed encapsulation and loading efficiencies were 62.9% and 0.82%, respectively. Cytotoxicity assay of this copolymer indicated no significant toxicity. CONCLUSION: Novel dual temperature‐ and pH‐sensitive Dex‐MA‐graft‐PNIPAAm nanoparticles may provide some advantages for anti‐cancer drug delivery due to a tunable LCST from 35 to 45 °C and controllable dimensions. These nanoscale materials could be excellent candidates for biotechnology and biomedical applications. Copyright © 2009 Society of Chemical Industry     

Studies on preparation and swelling properties of the N-isopropylacrylamide/chitosan semi-IPN and IPN hydrogels

Semi-interpenetrating network (semi-IPN) polymer gels and interpenetrating network (IPN) polymer gels with thermosensitivity were prepared by introducing a biodegradable polymer, chitosan, into the N-isopropyacrylamide (PNIPAAm) gel system. The swelling behavior, temperature sensitivity, pH sensitivity, gel strength, and drug-release behavior of PNIPAAm/chitosan semi-IPN and IPN hydrogels were investigated. The results indicated that the NIPAAm/chitosan semi-IPN and IPN hydrogels exhibited pH and temperature-sensitivity behavior and could slow drug release and diffusion from the gels. From the stress–strain curves of the hydrogels, the compression moduli of IPN gels containing crosslinked chitosan were higher than those of semi-IPN gels. This is because IPN gels have a more compact structure. The morphology of PNIPAAm/chitosan hydrogels was also investigated. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 82: 2487–2496, 2001