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-sensitive hydrogel based on carboxymethyl chitosan/sodium alginate and its application for drug delivery

Carboxymethyl chitosan sodium salt (CMCS)/sodium alginate (SA), a pH-sensitive hydrogel composed of CMCS and SA crosslinked by 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide, has been evaluated in vitro as a potential carrier for protein drug delivery of bovine serum albumin (BSA). The crosslinked structures, pore morphologies, and mechanical properties of the composite CMCS/SA hydrogel at different pH have been characterized by Fourier-transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and dynamic mechanical analysis (DMA). The swelling behavior of the prepared hydrogel was assessed at different pH values, 1.2, 4.0, 6.86, 7.4, and 9.0. The in vitro slow release ability of the CMCS/SA hydrogel was assessed at 37°C and pH 1.2 or pH 7.4 to simulate gastrointestinal and mouth environments in vivo. The efficiency was found to be greater than 90% at pH 7.4. The composite CMCS/SA hydrogel showed no cytotoxic effect toward L-929 cells according to the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test. These findings demonstrate that the composite hydrogel has promising potential for drug delivery. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 46911.     

Preparation of a novel pH-sensitive hydrogel based on acrylic acid and polyhedral oligomeric silsesquioxane for controlled drug release of theophylline

Hydrogels based on pH-sensitive polymers are of great interest as potential biomaterials for the controlled delivery of drug molecules. In this study, a novel pH-sensitive copolymer hydrogel based on acrylic acid (AA) monomer by free-radical solution polymerization were synthesized with organic–inorganic cross-linking agent of octavinyl polyhedral oligomeric silsesquioxane (OVPOSS). And its properties were compared with conventional hydrogels using N,N′-methylenebisacrylamide (MBA) as cross-linking agent. The copolymers were characterized by Fourier transform infrared spectra and differential scanning calorimetry. The morphology after swelling was presented by scanning electron microscopy. Swelling behaviors in different pH and potential applications in controlled drug delivery of the hydrogels were also examined. The results showed that both hydrogels were pH sensitive. However, as the addition of OVPOSS limited the movement of the molecular chain segment, the swelling ratio and the drug-release rate of theophylline in SGF decreased obviously when using OVPOSS as cross-linking agent, comparing with P(MBA-co-AA) hydrogels. The results in this study suggested that P(OVPOSS-co-AA) could serve as potential candidate for theophylline drug delivery.     

Microporous PDMAEMA‐based stimuli‐responsive hydrogel and its application in drug release

The microporous hydrogels (Pn‐Cm gels) composed of poly(dimethylaminoethyl methacrylate) and carboxymethylchitosan were synthesized in situ radical polymerization by using nano γ‐Fe₂O₃ particles as pore‐agent. The microporous structure formed through eliminating the Fe₂O₃ particles was designed to achieve a faster response rate and better drug loading effect. Comparing to the neat gels, Pn‐Cm gels exhibit deteriorative mechanical properties with the increased pores, while the gels still keep the elastic network structure which could bear some degree of tensile and compression deformation. Meantime, Pn‐Cm gels show similar temperature and pH double responsiveness with same isoelectric point shrink as that of neat gels, the swelling ability decreases slightly, and the deswelling rate increases with the increase of pores. Moreover, the 5‐fluorouracil was used as a target drug to explore the potential of this gel applied as drug‐release system. For Pn‐Cm gels, the more pores and carboxymethyl chitosan inside the gels are beneficial to the drug loading, all gels show a burst release of drug, being followed by a slow and sustained release with different rate. Comprehensively, the Pn‐Cm gels exhibit a better sustained release effect in the simulated stomach condition (pH = 2.1), the related release mechanism could be interpreted by the superposition of Fickian diffusion. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45326.     

聚天冬氨酸水凝胶合成及其应用于药物控释的研究进展

聚天冬氨酸是一种新型的聚合氨基酸材料,具有很好的生物相容性、生物降解性。本文综述了聚天冬氨酸及其衍生物水凝胶的研究现状,介绍了化学交联、光交联、γ射线交联3种交联方法合成的聚天冬氨酸及其衍生物水凝胶,以及近年来聚天冬氨酸基凝胶对大分子蛋白药物、小分子抗炎性药物、抗癌和基因药物控释的研究进展,并对该凝胶在药物控释领域的发展方向进行了预测。     

Preparation and in vitro controlled release behavior of a novel pH-sensitive drug carrier for colon delivery

The synthesis of a novel complex system designed for colon-targeting drug delivery was reported. The complex was prepared by dialdehyde konjac glucomannan and adipic dihydrazides to form steady Schiff base, and crosslinking with 5-aminosalicylic acid (5-ASA) through glutaraldehyde as a cross-linking agent. The structure was characterized by Fourier transform infrared (FTIR) spectroscopy, ¹³C NMR, wide angle X-ray diffraction (WAXRD) and thermogravimetric analysis. In vitro release of 5-ASA from the complex showed that the total released 5-ASA after 24 h in buffer solution at pH 1.2, 6.8, and 7.4 were 4, 59, and 21%, respectively. The release rate of 5-ASA can be controlled by tuning the pH value more effectively. The results indicated that the novel pH-sensitive complex could be potentially useful for colon-targeting drug delivery system.     

Formation of silk fibroin hydrogel and evaluation of its drug release profile

Silk hydrogels are interesting materials to be used as matrix in controlled drug delivery devices. However, methods to accelerate fibroin gelation and allow the drug incorporation during the hydrogel preparation are needed in literature. In this article we report the preparation of silk fibroin hydrogels with addition of several contents of ethanol, used to accelerate fibroin gelation kinetics, and we also evaluate the potential of these hydrogels to be used as matrices for drug delivery. Chemical and conformational properties did not change despite the amount of ethanol incorporated in the hydrogel. Hydrogels containing diclofenac sodium dissolved in ethanol showed a faster initial release of the drug than hydrogels with the drug dissolved in water but equilibrium was reached later. This indicates a more sustained drug delivery from hydrogels in which the model drug was dissolved in ethanol. Fibroin hydrogels confirm their promising use as biopolymeric matrices for controlled drug release. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41802.     

一种新型聚天冬氨酸水凝胶的制备及其药物缓释性能研究

介绍了一种新型羟化聚天冬氨酸-乙基纤维素(PASP-EC)互穿网络水凝胶的制备,研究了交联剂用量、乙醇胺用量及乙基纤维素(EC)用量对水凝胶溶胀性能的影响;同时,进行了水凝胶的pH敏感性测试,并以5-Fu为药物模型,研究其在肠液中(pH=7.4)的药物控释性能。实验结果表明,当己二胺、乙醇胺、EC的用量分别是聚琥珀酰亚胺(PSI)用量的3%、20%、30%时,水凝胶的溶胀性能最佳,达到290倍;且随着乙醇胺用量的增加,水凝胶在50%乙醇中的溶胀性能提高。pH敏感实验表明,羟化PASP-EC水凝胶具有pH敏感性。羟化PASP-EC水凝胶对5-Fu具有缓释效果,随着EC用量增加,缓释效果越明显。     

Preparation and swelling kinetics of pH-sensitive photocrosslinked hydrogel based on carboxymethyl chitosan

A series of photocrosslinkable carboxymethyl chitosans were synthesized by mixing azidobenzaldehyde and an aqueous solution of carboxymethyl chitosan. Aqueous solutions of the product were photocrosslinked via UV irradiation to afford hydrogels. The morphologies and the mechanical properties of the hydrogels were characterized. Their swelling kinetics were studied. The hydrogels displayed good pH sensitivity in pH 2.2–8.0 buffer solutions and an overshooting effect during swelling in pH <5 buffer solutions. The following three factors may contribute to this overshooting effect: firstly, because of the protonation of amide groups in the network in acidic solution, the formation of ionic bonds between amine ions and partial carboxylic ions causes the release of solvent from the swollen network; secondly, ionized carboxylic groups in the network become protonated and convert into nonionized carboxylic groups, and so the concentration of free counterions within the network gradually decreases in acidic solution, leading to solvent release; finally, hydrogen bonds gradually form between nonionized carboxylic groups on the network, which also leads to solvent release from the swollen network. In pH ≥ 5 buffer solutions, the overshooting effect disappeared and the swelling kinetics followed Schott’s second-order swelling kinetics.     

基于动态共价键的pH响应自修复水凝胶的制备与评价

以α-甲基丙烯酸(MAA)和2-丙烯酰胺-2-甲基丙磺酸(AMPS)的共聚物P(MAA/AMPS)及聚乙烯醇(PVA)为单体、十水合四硼酸钠为交联剂合成了P(MAA/AMPS)-PVA二重互穿网络的pH响应水凝胶.通过SEM、FTIR、GPC、TGA-DTG和流变仪等表征了水凝胶的表面形貌和化学状态;测定了水凝胶的溶胀性﹑pH响应性﹑自修复性和流变性.结果表明,水凝胶形成了稳定的互穿网络结构且具有pH敏感性、自修复性;PVA羟基与硼酸根离子形成的共价配位硼酸酯键使水凝胶具备自修复性并受介质酸碱性的控制;力学性能测定结果显示,自修复水凝胶(SB用量为2.5％,水凝胶溶胀度为4)拉伸强度668 kPa,断裂伸长率可达665％,修复效率可达81％.     

基于动态共价键的pH响应自修复水凝胶制备与评价

以α-甲基丙烯酸、2-丙烯酰胺-2-甲基丙磺酸共聚产物和聚乙烯醇为单体，十水合四硼酸钠为交联剂合成P(MAA /AMPS)-PVA二重互穿网络的pH响应水凝胶；通过扫描电子显微镜(SEM)、红外光谱(FTIR)、凝胶渗透色谱（GPC）、热重分析(DSC-TG)和流变仪等表征了水凝胶的表面形貌和化学状态；测定了水凝胶的溶胀性﹑pH响应性﹑自修复性和流变性。结果表明，水凝胶形成稳定的IPN互穿网络结构且该水凝胶具pH敏感性、自修复性；PVA羟基与硼酸根离子形成的共价配位硼酸酯键决定水凝胶自修复性并受到介质酸碱控制；力学性能测定结果显示，自修复水凝胶拉伸强度668 kPa,断裂伸长率可达665%，修复效率可达81%。     

A facile preparation of pH‐temperature dual stimuli‐responsive supramolecular hydrogel and its controllable drug release

A series of pH‐temperature dual stimuli‐responsive random copolymers poly[N,N‐dimethylaminoethyl methacrylate‐co‐poly(poly(ethylene glycol) methyl ether methacrylate][poly(DMAEMA‐co‐MPEGMA)] were synthesized by free radical polymerization. The supramolecular hydrogel was formed by pseudopolyrotaxane, which was prepared with the host‐guest interactions between α‐cyclodextrin (α‐CD) and poly(ethylene glycol) (PEG) side chains. Fourier transform infrared (FT‐IR), nuclear magnetic resonance (¹H NMR), and X‐ray diffraction (XRD) confirmed the structures of the hydrogels. The pH‐temperature dual stimuli responsive properties of the hydrogels were characterized by rheometer. Finally, the controllable drug release behavior of the hydrogel, which was used 5‐fluorouracil (5‐Fu) as the model drug, was investigated at different temperatures and different pH values. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43279.     

pH-sensitive IPN hydrogel based on poly (aspartic acid) and poly (vinyl alcohol) for controlled release

Various pH-sensitive sequential interpenetrating polymer network (IPN) hydrogels were prepared by introducing poly (vinyl alcohol) (PVA) hydrogel into Poly (aspartic acid) (PASP) hydrogel by freeze-thawing treatment to obtain a novel drug delivery system to the intestine. The structure and the morphologies of the prepared hydrogels were studied by Fourier Transform Infrared Spectroscopy (FTIR) and scanning electron microscopy (SEM). The thermal behavior and crystallinity of the hydrogels were characterized by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Their pH-sensitive properties moreover were studied and the results revealed that both PASP hydrogel and IPN hydrogels exhibited excellent pH-sensitivity. Furthermore, the controlled drug release properties of the hydrogels were also evaluated and results indicated that by increasing the PVA fraction in the IPN hydrogel, the release of Naproxen sodium was improved. These results show that the IPN hydrogels could be a suitable carrier for site-specific drug delivery in the intestine.     

Synthesis and characterization of a novel pH-responsive nanocomposite hydrogel based on chitosan for targeted drug release

Over the last decade, nanocomposite hydrogels have been provided a new approach for the biomedical field. In this work, a novel pH-responsive nanocomposite hydrogel was fabricated using simultaneous in situ formation of magnetite iron oxide nanoparticles and hydrogel networks of poly(acrylic acid) grafted onto chitosan. The effects of various types of precursor molecules, pH, salt, and loading pressure were examined on the swelling properties of resulting nanocomposite hydrogels. The synthesized nanocomposite hydrogel was well characterized using different instruments. In vitro drug releasing behavior of doxorubicin was studied at pH 5.4 and 7.4. The drug release mechanism was investigated through different kinetic models. These experimental results open a new opportunity to make pH-responsive nanocomposite hydrogel devices for controlled delivery of drug.     

A rechargeable drug delivery system based on pNIPAM hydrogel for the local release of curcumin

This study was designed to develop a drug delivery system based on poly(N-isopropylacrylamide) (pNIPAM) hydrogel and a suitable solvent to enhance solubility and local release of curcumin. pNIPAM hydrogel was synthesized by radical polymerization. The chemical, mechanical and physical properties and biocompatibility of pNIPAM hydrogel were investigated as an implantable and rechargeable drug reservoir. Curcumin was loaded within pNIPAM hydrogel during swelling by using two different solvents; methanol, an organic solvent, and low molecular weight polyethylene glycol (PEG200), a polymeric solvent. The results of drug solubility showed that using PEG200 can increase curcumin solubility more than commonly used organic solvents such as methanol. Also, the release profile of drug-loaded hydrogels demonstrated that PEG200 has a superior effect on the cumulative amount of released curcumin (33.163 ± 0.319 μg/ml) compared to methanol (8.765 ± 0.544 μg/ml) during 1 week. Based on our results, curcumin-loaded hydrogels did not show any cytotoxicity, and pNIPAM/PEG combination represented an antibacterial effect within 12 hours. Accordingly, it can be concluded that pNIPAM hydrogel in combination with low molecular weight PEG200 could be used as an efficient drug delivery system to preserve and provide sustained release of curcumin as a hydrophobic drug.     

基于大环化合物主-客体作用的超分子聚合物凝胶材料研究进展

综述了近年来冠醚、环糊精、葫芦脲和柱芳烃等大环化合物的衍生物通过主-客体作用形成的超分子聚合物凝胶材料的研究情况。指出了该材料对温度、酸碱度、溶剂和客体分子等外界环境刺激敏感,在智能响应性方面表现出了优异的性质。对超分子聚合物凝胶材料未来的研究方向进行了展望。     

基于大环化合物主-客体作用的超分子聚合物凝胶材料研究进展

综述了近年来冠醚、环糊精、葫芦脲和柱芳烃等大环化合物的衍生物通过主-客体作用形成的超分子聚合物凝胶材料的研究情况。指出了该材料对温度、酸碱度、溶剂和客体分子等外界环境刺激敏感,在智能响应性方面表现出了优异的性质。对超分子聚合物凝胶材料未来的研究方向进行了展望。     

Interpenetrating hydrogel networks based on gelatin and polyacrylamide: Synthesis,swelling, and drug release analysis

Interpenetrating hydrogel network has been synthesized from gelatin and polyacrylamide by cross-linking with their respective cross-linking agents. The swelling behavior of this Interpenetrating polymer network (IPN) system was analyzed in water and in citric acid-phosphate buffer solution at various pH. The effect of temperature on swelling behavior of these gels has been analyzed by variation from 25 to 60°C at physiological pH. The drug release behavior of these gels was also analyzed with temperature variation at physiological pH. © 1994 John Wiley & Sons, Inc.     

Synthesis and characterization of polysaccharide hydrogel based on hydrophobic interactions

Hydrogels based on hydrophobic, or micellar interactions, are physically crosslinked hydrogels which are an attempt to overcome the poor mechanical properties of traditional, chemically crosslinked gels, such as low shear strength. We have prepared a polysaccharide-based hydrogel with physical crosslinks via hydrophobic interactions. In this work, we have synthesized hydrogel by grafting a hydrophobic moiety dioctylamine onto hydrophilic precursor carboxymethyl cellulose (CMC) through an amide bond formation, where ~33% of the carboxyl group in CMC was reacted with dioctylamine. The thermosensitive hydrogel can arrest 100 mL of deionized water per gram of gelator within few seconds. It showed the moderate rheological property. The hydrogel is nontoxic and does not show any adverse to human hemoglobin. It is a CMC based a unique gelator with high biocompatibility represent to be useful materials for biomedical application. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47665.