新型离子交联聚两性电解质水凝胶的研究
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摘要
电场敏感水凝胶易于调控、响应方式多样、可精确控制载附药物的释放,因此在药物的控制释放领域有潜在的应用前景。离子交联聚两性电解质水凝胶上有带正负两种电荷的基团,在正负电荷之间形成了离子交联。离子交联键与共价键相比,属于弱的相互作用,对环境的变化更为敏感。因此,离子交联的聚两性电解质水凝胶可能具有独特的电场响应行为,有可能开发为电场控释给药载体材料。
本论文完成的主要工作如下:
(1)通过酸性单体与碱性单体之间的质子转移反应,制备了丙烯酸(AAc)与丙烯酸二乙胺基乙酯(DEAEM)以及2-丙烯酰胺-2-甲基丙磺酸(AMPS)与丙烯酸二乙胺基乙酯(DEAEM)离子复合物。FTIR图谱证实离子复合物中存在类叔铵盐的交联结构。
(2)上述两类离子复合物分别与丙烯酰胺(AAm)水溶液自由基共聚反应,在没有化学交联剂的情况下,制备了两类离子交联聚两性电解质水凝胶:P(AAc/DEAEM/AAm)凝胶(简称PADA凝胶)和P(AMPS/DEAEM/AAm)凝胶(简称AMDA凝胶)。凝胶在接触电场下表现出溶胀/溶蚀的双重响应行为。盐溶液的浓度和种类、电极、电压等对该响应行为有较大的影响。
(3)实验表明,凝胶的接触电场行为分为溶胀和消溶胀两个阶段。在电场的作用下,凝胶先发生溶胀,当离子交联结构被破坏后,凝胶发生溶蚀。动力学研究表明,溶胀可能受到外加电场的影响;而凝胶的溶蚀则是零级动力学过程。
(4)以柳氮磺吡啶和甲巯咪唑为模型药物,研究了载药凝胶的药物释放规律。盐浓度、pH值以及载药方式直接影响药物释放。电场实验表明外加电场能够促进药物释放。对比了正极导入、负极导入对药物透凝胶薄膜的影响。一定电流强度下,正极导入效果优于负极导入。
上述结果表明离子交联聚两性电解质水凝胶有可能开发为电场控释给药载体材料,但凝胶性质的优化、电场装置的设计、给药条件的确定等方向还有待进一步研究。
Eelectro-responsive hydogels have advantages such as the availability of equipment that allows precise control with regards to the magnitude of current, various manner of responsiveness, precise controlling over drug release, they might be used in the field of controlled drug delivery. Ionic crosslinked polyampholyte hydrogels containing both positive and negative charged groups, ionic crosslinkage have fromed between positive and negative charged groups. Compared with covalent bonding, ionic bonding belongs to weak interaction. Consequently, it was more sensitive to the ambient solutions. So this ionic crosslinked polyampholyte hydrogel may have dual stimulating response behavior, they might be used for electro-controlling drug delivery material. The main contents are as follows.
(1) The ionic complex was formed by the proton-transfer reaction between acidic monomer (acrylic acid, AAc or 2-acrylamide-2-methyl propane sulfonic acid, AMPS) and basic monomer ((N,N-diethylamino)ethyl methacrylate, DEAEM). The FTIR spectra of the ionic complexion confirmed the proton-transfer reaction between acidic monomer and basic monomer.
(2) Through the radical copolymerization of ionic complexion and acrylamide (AAm), the ionic crosslinked polyampholyte hydrogels, Two novel type of ionic crosslinked polyampholyte hydrogels (PADA, AMDA gel), were prepared in the absent of chemical crosslinker. Gels exhibited dual electro-responsiveness behavior under contact DC field: swelling and eroding. The voltage, the species and concentration of electrolyte, connect to different electrode and some other factors have great effect on the swelling/erosion behavior of gels.
(3) The results showed that gels have two responsive stages (swelling stage and eroding stage) in contacted DC field. Gels swelled firstly, when the ionic crosslinkage was dissociated, gels started to occur eroding. The kinetic study on the swelling/eroding behavior demonstrated that the swelling was possibly affected by additional electric field, and the eroding followed zero-order kinetics.
(4) The drug release rule of the drug loading gels was briefly researched. Concentration of the NaCl solution, pH of PBS solution and drug loading method had directly affection on the drug release behavior. Electric experiment showed that additional electric field can accelerate drug release. The affection of anode and cathode on drug delivery through the gel membrane were compared, the results showed that anode inductive drug delivery was better than cathode inducting.
The total results showed that developing polyampholyte hydrogels into electro-controlling drug delivery material have great potential. But it has much work to accomplish, such as optimizing gel’s property, designing the electric device, selecting condition of drug delivery, and forth and so on.
本论文完成的主要工作如下:
(1)通过酸性单体与碱性单体之间的质子转移反应,制备了丙烯酸(AAc)与丙烯酸二乙胺基乙酯(DEAEM)以及2-丙烯酰胺-2-甲基丙磺酸(AMPS)与丙烯酸二乙胺基乙酯(DEAEM)离子复合物。FTIR图谱证实离子复合物中存在类叔铵盐的交联结构。
(2)上述两类离子复合物分别与丙烯酰胺(AAm)水溶液自由基共聚反应,在没有化学交联剂的情况下,制备了两类离子交联聚两性电解质水凝胶:P(AAc/DEAEM/AAm)凝胶(简称PADA凝胶)和P(AMPS/DEAEM/AAm)凝胶(简称AMDA凝胶)。凝胶在接触电场下表现出溶胀/溶蚀的双重响应行为。盐溶液的浓度和种类、电极、电压等对该响应行为有较大的影响。
(3)实验表明,凝胶的接触电场行为分为溶胀和消溶胀两个阶段。在电场的作用下,凝胶先发生溶胀,当离子交联结构被破坏后,凝胶发生溶蚀。动力学研究表明,溶胀可能受到外加电场的影响;而凝胶的溶蚀则是零级动力学过程。
(4)以柳氮磺吡啶和甲巯咪唑为模型药物,研究了载药凝胶的药物释放规律。盐浓度、pH值以及载药方式直接影响药物释放。电场实验表明外加电场能够促进药物释放。对比了正极导入、负极导入对药物透凝胶薄膜的影响。一定电流强度下,正极导入效果优于负极导入。
上述结果表明离子交联聚两性电解质水凝胶有可能开发为电场控释给药载体材料,但凝胶性质的优化、电场装置的设计、给药条件的确定等方向还有待进一步研究。
Eelectro-responsive hydogels have advantages such as the availability of equipment that allows precise control with regards to the magnitude of current, various manner of responsiveness, precise controlling over drug release, they might be used in the field of controlled drug delivery. Ionic crosslinked polyampholyte hydrogels containing both positive and negative charged groups, ionic crosslinkage have fromed between positive and negative charged groups. Compared with covalent bonding, ionic bonding belongs to weak interaction. Consequently, it was more sensitive to the ambient solutions. So this ionic crosslinked polyampholyte hydrogel may have dual stimulating response behavior, they might be used for electro-controlling drug delivery material. The main contents are as follows.
(1) The ionic complex was formed by the proton-transfer reaction between acidic monomer (acrylic acid, AAc or 2-acrylamide-2-methyl propane sulfonic acid, AMPS) and basic monomer ((N,N-diethylamino)ethyl methacrylate, DEAEM). The FTIR spectra of the ionic complexion confirmed the proton-transfer reaction between acidic monomer and basic monomer.
(2) Through the radical copolymerization of ionic complexion and acrylamide (AAm), the ionic crosslinked polyampholyte hydrogels, Two novel type of ionic crosslinked polyampholyte hydrogels (PADA, AMDA gel), were prepared in the absent of chemical crosslinker. Gels exhibited dual electro-responsiveness behavior under contact DC field: swelling and eroding. The voltage, the species and concentration of electrolyte, connect to different electrode and some other factors have great effect on the swelling/erosion behavior of gels.
(3) The results showed that gels have two responsive stages (swelling stage and eroding stage) in contacted DC field. Gels swelled firstly, when the ionic crosslinkage was dissociated, gels started to occur eroding. The kinetic study on the swelling/eroding behavior demonstrated that the swelling was possibly affected by additional electric field, and the eroding followed zero-order kinetics.
(4) The drug release rule of the drug loading gels was briefly researched. Concentration of the NaCl solution, pH of PBS solution and drug loading method had directly affection on the drug release behavior. Electric experiment showed that additional electric field can accelerate drug release. The affection of anode and cathode on drug delivery through the gel membrane were compared, the results showed that anode inductive drug delivery was better than cathode inducting.
The total results showed that developing polyampholyte hydrogels into electro-controlling drug delivery material have great potential. But it has much work to accomplish, such as optimizing gel’s property, designing the electric device, selecting condition of drug delivery, and forth and so on.
引文
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[2]刘锋,卓仁禧.水凝胶的制备及应用[J].高分子通报, 1995, 4: 205~215
[3]李志军,王振武,宋宏立.智能水凝胶的研究进展[J].化学工业与工程技术, 2006, 27(1): 6~11
[4] Lehto J, Vaaramaa K, Vesteinen E, et al. Uptake of zinc, nickel, and chromium by N-isopropylacrylamide polymer gels[J]. J Appl polym Sci, 1998, 68(3):355~362.
[5] Schmedlen R H, Masters K S, West J F. Photocrosslinkable polyvinyl alcohol hydrogels that can be modified with cell adhesion peptides for use in tissue engineering [J]. Biomaterials, 2002, 23(22): 4325~4332
[6] Berger J, Reist M. Structure and interactions in chitosan hydrogels formed by complexation or aggregation for biomedical applications [J]. European Journal of Pharmaceutics and Biopharmaceutics, 2004, 57(1): 35~52
[7] Tanaka T, Fillmore D, Sun S, et al. Phase transitions in ionic gels [J]. Physical Review Letters, 1980, 45(20): 1636~1639
[8]陈文明,阎立峰. P(AAcoDMMC)水凝胶的γ辐射合成及pH响应行为[J].核技术, 2000, 23(8): 545~547.
[9]张建合,杨亚江.亲水/疏水互穿网络水凝胶的合成及其pH敏感特性研究[J].信阳师范学院学报(自然科学版), 1999, 12(4): 440~443
[10]陆大年,陈士安.丙烯酸水凝胶的pH敏感性研究[J].华东理工大学学报, 1994, 20(6): 818~823
[11]徐晖,丁平田.药物在pH敏感甲基丙烯酸-poloxamer水凝胶中的扩散行为[J].应用化学, 2001, 18(4): 305~308
[12] Sieggel R A, Falamrsian M, Firestone B A, et al. PH controlled release form hydrophobic/polyelectrolyte co-polymer hydrogels [J]. J Controlled Release, 1998,8(3): 179~182
[13] Shi L L, Yang L M, Chen J, et al. Preparation and characterization of pH sensitive hydrogel of chitosan/ poly(acrylicacid)co-polymer[J]. Journal of Biomaterial Science, Polymer Edition, 2004, 15(4): 465~474
[14] Pei Y, Chen J, Yang L M, et al. The effect of pH on LCST of Poly(N-isopropyl -acrylamide) and Poly(N-isopropylacrylamide-co-acrylicacid[J]. Journal of Biomaterial Science, 2004, 15(5): 585~594
[15] Tanaka T, Hirokawa Y. Volume-phase transitions of ionized N-isopropylacrylamide gels[J]. Chem Phys, 1987, 81(2): 1392~1395
[16] Beltran S. Swelling equilibria for ionized temperature sensitive gels in water and inaqueous salt solutions[J]. Chem Phys, 1990, 92: 2061~2066
[17] Winnik F M. Fluorescence studies of aqueous solutions of poly(N-iso -propylacrylamide) below and above their LCST[J]. Macromolecules, 1990, 23: 233~242
[18] Schild H G, Tirrell D A. Microcalorimetric detection of lower critical solution temperatures in aqueous polymer solutions [J]. J Phys Chem, 1990, 94: 4352~4356
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