氨基糖类衍生物智能水凝胶作为药物载体的研究
|
摘要
水凝胶由于具有丰富的交联网络结构和良好的可膨胀性,被广泛用作缓释药物的载体。本文利用具有生物相容性的氨基葡萄糖单糖衍生物、具有温敏性的异丙基丙烯酰胺(NIPAM)及具有pH敏感性的丙烯酸(AAc)共聚得到了全新的微凝胶,新型微凝胶具有良好的生物相容性、组织靶向性和对温度、pH的刺激响应性。利用天然的氨基多糖衍生物和端基活化的聚乙二醇在生理条件下,自组装得到了大孔凝胶,这种天然氨基多糖凝胶也具备某种温敏的特征。两种凝胶负载胰岛素和牛血清白蛋白(BSA)等生物大分子药物的实验均显示了良好的智能释药性能,有望成为新型的智能给药系统。
一、凝胶的制备
1.氨基葡萄糖单糖衍生物微凝胶的制备
通过使用水溶性缩合剂联合诱导酰胺化反应合成了氨基葡萄糖单糖衍生物—丙烯酰氨基葡萄糖(AADG)。将AADG,NIPAM及AAc作为反应单体,用自由基沉淀聚合法制备了微凝胶。
2.天然氨基多糖衍生物大孔凝胶的制备
合成了四种具有可活化巯基型端基的聚乙二醇(PEG)交联剂,分别是:丙烯酰化、溴化、碘化及马来酸酐化端基的PEG交联剂,这些交联剂可通过端基与天然氨基多糖衍生物—巯基壳聚糖(CS-NAC)上的巯基在生理条件下自然发生迈克尔加成反应,进而形成凝胶。
二、凝胶的表征
1.粒径及分布
实验结果表明,干态的微凝胶具有近乎球形的形态,粒径为50～60 nm左右,湿态的微凝胶粒径为100 nm左右,且分布比较均一。
2.孔径
通过扫描电子显微镜可以看到凝胶内部呈现多孔的类似海绵内部的结构,孔径在10μm左右,浸泡24h后可以发现网络结构发生了降解,孔径变大,达到20μm左右,浸泡7d后凝胶进一步降解,孔径增大到40～50μm。
3.热稳定性
通过热重实验表明壳聚糖-PEG凝胶的热失重过程主要包括两个阶段,分别对应于壳聚糖碳链的分解及PEG碳链的分解,并且由于壳聚糖刚性链对PEG结晶行为的抑制,改变了PEG失重特征峰的位置,而PEG并未对壳聚糖的失重特征峰产生影响。
4.机械强度
对凝胶进行了振荡应力扫描及频率扫描,结果表明,凝胶内部的交联密度越大,对应的弹性及机械强度也就越大,因此可以在制备凝胶时调整原料的类别和用量来控制凝胶的机械强度。
5.溶胀及降解
凝胶在37℃时快速溶胀,半个小时内就达到了最大的溶胀平衡,而在25℃时,需4h才达到。随后的24h内凝胶都快速的降解,在这之后降解逐渐缓慢下来,在6周后凝胶还未完全降解。内部交联密度的大小决定了凝胶的最大平衡溶胀度及降解速度。
三、凝胶的智能释药与生物相容性
1.温敏特性
随着温度的升高,微凝胶的粒径有了显著的增大,表现在药物释放上,同一pH下,41℃时有明显的突释现象,2h释放了88%的药物,而在37℃时释放缓慢,2d后才释放了79%的药物。
大孔凝胶对温度的敏感性也很显著,凝胶在25℃时的最大平衡溶胀度比37℃时降低了约四分之一,表现在药物释放上,37℃时3d之内药物已经释放完全,而在25℃时3d才释放不到60%的药物。
2.pH敏特性
当pH值小于5.0时,微凝胶的有效粒径几乎不变,而当pH值大于5.0时,粒径随着pH值的增大而增大,表现在药物释放上,同一温度下,pH 6.9时,2h释放了88%的药物,而pH 7.4时,3 h释放了79%的药物。微凝胶的pH敏特性并不如温敏特性显著,是因为在高的pH值下羧基的离子化使相变的温度范围变宽。
3.组织靶向性
微凝胶在肿瘤环境条件下呈现两个阶段的药物释放,初始的突释及其后的缓慢释放;而在正常生理条件下则始终是平缓的释放过程,这说明微凝胶在肿瘤环境条件下具有更快速的初始释放速率。
大孔凝胶的形成时间受巯基壳聚糖的巯基含量、浓度,交联剂的端基类型、分子量、用量,以及反应的温度影响。凝胶固化时间的可控也使宏观形态的凝胶具有了“靶向性”,可以通过不同作用部位来选用不同固化时间的凝胶,确保凝胶在到达作用部位后立即固化。
4.生物相容性
细胞毒性实验表明两种凝胶都具有良好的细胞增殖能力,其中大孔凝胶的细胞培养实验说明了细胞可以通过凝胶的孔道而迁移至凝胶的内部生长,并且细胞的生长状态良好,说明这种新型凝胶除作为药物载体外,还有作为细胞支架潜力,可进一步应用于组织工程中。
圆二色及凝胶电泳实验表明了两种凝胶都很好的保持了所包载的蛋白质药物的活性。
四、智能释药机理初步探讨
1.收缩
微凝胶初始的突释可能是由于水分子与NIPAM中亲水的酰胺基团形成的氢键断开造成的,同时NIPAM中疏水的异丙基基团开始互相吸引,微凝胶表面疏水性增强,进而发生相转变并快速收缩使药物急剧释出,这形成了一种类似快速扩散的行为。
2.溶胀
使用半经验的数学模型拟合药物释放过程,证明凝胶的药物释放机理属于Fick扩散机理,并且推断出药物释放属于溶胀支配型药物释放,因此凝胶内部结构的紧密程度决定了不同凝胶药物释放的快慢。
3.降解
凝胶的降解并未对释放产生明显的影响,这可能是因为药物的尺寸(BSA,d_h=7.2 nm)远远小于凝胶的孔径(10μm)。
Due to plentiful crosslinking network and favorable expansibility,hydrogels have been studied extensively for application as drug delivery carrier.In the present study,a novel microgel was designed by the incorporation of temperature sensititive N-isopropylacrylamide(NIPAM) and pH sensitive acrylic acid(AAc) to copolymerize with glucosamine derivative,acrylamido-2-deoxy-glucose(AADG). The novel microgel has favorable biocompatibility,tissue-targeting and stimuli-responsibility to pH and temperature.Moreover,a novel in situ cross-linked hydrogel was prepared under physiological conditions,based on self-assembly of natural amino polysaccharide derivatives with homo-bifunctional PEG derivatives using Michael type addition,and the natural amino polysaccharide hydrogel also has some temperature sensitivity.The in vitro macromolecular drug delivery experiment suggested the favorable intelligent drug release abilities of these two gels,and they have potential to be novel intelligent drug delivery system.
Ⅰ.Preparation of gels
1.Preparation of glucosamine derivative microgel
Acrylic acid was attached to glucosamine via an amide bond between the carboxylic group and a free primary group.The microgels of the obtained functional glucosamine-AADG with NIPAM and AAc as the comonomer were prepared by the method of a free radical precipitation polymerization.
2.Preparation of natural amino polysaccharide hydrogel
Four homo-bifunctional PEG derivatives were synthesized:acrylate,bromoacetate, iodoacetate and maleimide functional PEG..And they were examined as cross-linking agents for thiol-modified derivatives of chitosan.The hydrogels were prepared by Michael type addition between the bifunctional PEG derivatives and thiol-modified chitosan.
Ⅱ.Characterization of gels
1.Size and morphology of microgel
The morphology of the resulting microgel was investigated by SEM.It is evident that microgels are well dispersed as individual particles with spherical shapes.It can be seen that the size of the microgels is around 50～60 nm in diameter in the solid state,and the microgels exhibit a narrow size distribution with an average diameter of around 100 nm in the wet state.
2.Pore size and morphology of hydrogel
The SEM images of freeze-dried hydrogels exhibited a highly macroporous spongelike structure and the average mesh size is about 10μm.After being dipped in PBS for 24 h and 7 d,the chains in the network degraded and the pores of the hydrogel increased
3.Thermal stability of hydrogel
All the hydrogels showed a two-stage thermal decomposition,the first-stage decomposition temperature was similar to that of chitosan,suggesting the introduction of PEG via Michael type addition did not decrease thermal stability of chitosan.And the weight loss results in the second-stage thermal decomposition were similar to the contents of PEG in hydrogels and indicate that the second-stage decomposition was caused by PEG.The second-stage degradation temperature increased when decreasing the content of PEG,which may be due to the inhibition of crystal growth of PEG caused by the stiff chitosan chain.
4.Rheology
The resulting of oscillatory stress sweep and frequency sweep indicated the higher mechanical strength and elasticity of hydrogel can be achieved by increasing the cross-linking density.
5.Swelling and degradation
All the hydrogels swelled rapidly and reached equilibrium within 0.5 h at 37℃, but within 4 h at 25℃.After reaching swelling equilibrium,all the hydrogels were rapidly degraded in the first 24 h,and then the degradation became slowly and hydrogels did not completely dissolve within six weeks.
Ⅲ.Intelligent drug release and biocompatibility of gels
1.Temperature sensitivity
The results of dynamic light scattering measurement show that the size of the microgels significantly increased with an increase in the temperature.And drug release profile represents the temperature sensitivity,under the same pH value,at 41℃,about 88%of drug was released within the initial 2 h;at 37℃,only about 79% of drug was released after 2 d.
The temperature sensitivity of hydrogel is also remarkable,the equilibrium swelling ratio of hydrogel at 25℃decreased to 25%of that at 37℃.For drug release profile,at 37℃,drug was completely released within 3 d;at 25℃,only about 60%of drug was released after 3 d.
2.pH sensitivity
When pH＜5.0,the diameters of microgels were nearly invariable regardless of the change of pH,and when pH≥5.0,the diameters became larger when the pH value was increased.And drug release profile represents the pH sensitivity,under the same temperature,at pH 6.9,about 88%of drug was released within the initial 2 h;at pH 7.4,about 79%drug was released within the initial 3 h.
3.Tissue-targeting
The drug release from microgel was two-stage under the tumor-surrounding environment,the initial burst release and subsequent slow release;and for the drug release under physiological conditions,the diffusing process was sustained slow and mild.Therefore,the release of drug at the tumor-surrounding environment is faster than that under normal physiological conditions.
The gelation time of hydrogel was determined by the thiols contents and concentration of CS-NAC,the terminal group type,molecular weight and the amount of cross-linking agents,and the reaction temperature.The controllability of hydrogel gelation time make macro form gel have tissue-targeting ability.
4.Biocompatibility
The cell viability study showed that the use of glucosamine may improve the biocompatibility of the microgels.The cell culture results illustrate that cells can migrate into the hydrogel networks and remain viable and maintain their 3D morphology during the 3 days culture.
The secondary structures of insulin and BSA as determined by CD spectra and SDS-PAGE were preserved in all gels.
Ⅵ.Mechanism of intelligent drug release
1.Shrinkage
The drug release from microgel has an initial burst,which was correlated to the NIPAM segment in the microgels.As the temperature increased up to a certain point, the water contained in the microgels was expelled due to the disruption of hydrogen bonding between water and the hydrophilic amide groups,then the hydrophobic isopropyl groups began to associate.And following the structural change and consequent enhanced surface hydrophobicity,the microgels shrunk and aggregated, the insulin was squeezed out.
2.Swelling
Fitted by semi-empirical mathematical model,mechanism of drug release from hydrogel was determined for Fick diffusion,and the release type was belong to swelling dominating drug release by further inference.Therefore,the crosslinking density determined the release rate of different hydrogels.
3.Degradation
Degradation of hydrogel did not have significant effect on drug release,which may be due to the huge difference between hydrodynamic diameter of BSA(d_h=7.2 nm) and hydrogel pore size(10μm).
一、凝胶的制备
1.氨基葡萄糖单糖衍生物微凝胶的制备
通过使用水溶性缩合剂联合诱导酰胺化反应合成了氨基葡萄糖单糖衍生物—丙烯酰氨基葡萄糖(AADG)。将AADG,NIPAM及AAc作为反应单体,用自由基沉淀聚合法制备了微凝胶。
2.天然氨基多糖衍生物大孔凝胶的制备
合成了四种具有可活化巯基型端基的聚乙二醇(PEG)交联剂,分别是:丙烯酰化、溴化、碘化及马来酸酐化端基的PEG交联剂,这些交联剂可通过端基与天然氨基多糖衍生物—巯基壳聚糖(CS-NAC)上的巯基在生理条件下自然发生迈克尔加成反应,进而形成凝胶。
二、凝胶的表征
1.粒径及分布
实验结果表明,干态的微凝胶具有近乎球形的形态,粒径为50～60 nm左右,湿态的微凝胶粒径为100 nm左右,且分布比较均一。
2.孔径
通过扫描电子显微镜可以看到凝胶内部呈现多孔的类似海绵内部的结构,孔径在10μm左右,浸泡24h后可以发现网络结构发生了降解,孔径变大,达到20μm左右,浸泡7d后凝胶进一步降解,孔径增大到40～50μm。
3.热稳定性
通过热重实验表明壳聚糖-PEG凝胶的热失重过程主要包括两个阶段,分别对应于壳聚糖碳链的分解及PEG碳链的分解,并且由于壳聚糖刚性链对PEG结晶行为的抑制,改变了PEG失重特征峰的位置,而PEG并未对壳聚糖的失重特征峰产生影响。
4.机械强度
对凝胶进行了振荡应力扫描及频率扫描,结果表明,凝胶内部的交联密度越大,对应的弹性及机械强度也就越大,因此可以在制备凝胶时调整原料的类别和用量来控制凝胶的机械强度。
5.溶胀及降解
凝胶在37℃时快速溶胀,半个小时内就达到了最大的溶胀平衡,而在25℃时,需4h才达到。随后的24h内凝胶都快速的降解,在这之后降解逐渐缓慢下来,在6周后凝胶还未完全降解。内部交联密度的大小决定了凝胶的最大平衡溶胀度及降解速度。
三、凝胶的智能释药与生物相容性
1.温敏特性
随着温度的升高,微凝胶的粒径有了显著的增大,表现在药物释放上,同一pH下,41℃时有明显的突释现象,2h释放了88%的药物,而在37℃时释放缓慢,2d后才释放了79%的药物。
大孔凝胶对温度的敏感性也很显著,凝胶在25℃时的最大平衡溶胀度比37℃时降低了约四分之一,表现在药物释放上,37℃时3d之内药物已经释放完全,而在25℃时3d才释放不到60%的药物。
2.pH敏特性
当pH值小于5.0时,微凝胶的有效粒径几乎不变,而当pH值大于5.0时,粒径随着pH值的增大而增大,表现在药物释放上,同一温度下,pH 6.9时,2h释放了88%的药物,而pH 7.4时,3 h释放了79%的药物。微凝胶的pH敏特性并不如温敏特性显著,是因为在高的pH值下羧基的离子化使相变的温度范围变宽。
3.组织靶向性
微凝胶在肿瘤环境条件下呈现两个阶段的药物释放,初始的突释及其后的缓慢释放;而在正常生理条件下则始终是平缓的释放过程,这说明微凝胶在肿瘤环境条件下具有更快速的初始释放速率。
大孔凝胶的形成时间受巯基壳聚糖的巯基含量、浓度,交联剂的端基类型、分子量、用量,以及反应的温度影响。凝胶固化时间的可控也使宏观形态的凝胶具有了“靶向性”,可以通过不同作用部位来选用不同固化时间的凝胶,确保凝胶在到达作用部位后立即固化。
4.生物相容性
细胞毒性实验表明两种凝胶都具有良好的细胞增殖能力,其中大孔凝胶的细胞培养实验说明了细胞可以通过凝胶的孔道而迁移至凝胶的内部生长,并且细胞的生长状态良好,说明这种新型凝胶除作为药物载体外,还有作为细胞支架潜力,可进一步应用于组织工程中。
圆二色及凝胶电泳实验表明了两种凝胶都很好的保持了所包载的蛋白质药物的活性。
四、智能释药机理初步探讨
1.收缩
微凝胶初始的突释可能是由于水分子与NIPAM中亲水的酰胺基团形成的氢键断开造成的,同时NIPAM中疏水的异丙基基团开始互相吸引,微凝胶表面疏水性增强,进而发生相转变并快速收缩使药物急剧释出,这形成了一种类似快速扩散的行为。
2.溶胀
使用半经验的数学模型拟合药物释放过程,证明凝胶的药物释放机理属于Fick扩散机理,并且推断出药物释放属于溶胀支配型药物释放,因此凝胶内部结构的紧密程度决定了不同凝胶药物释放的快慢。
3.降解
凝胶的降解并未对释放产生明显的影响,这可能是因为药物的尺寸(BSA,d_h=7.2 nm)远远小于凝胶的孔径(10μm)。
Due to plentiful crosslinking network and favorable expansibility,hydrogels have been studied extensively for application as drug delivery carrier.In the present study,a novel microgel was designed by the incorporation of temperature sensititive N-isopropylacrylamide(NIPAM) and pH sensitive acrylic acid(AAc) to copolymerize with glucosamine derivative,acrylamido-2-deoxy-glucose(AADG). The novel microgel has favorable biocompatibility,tissue-targeting and stimuli-responsibility to pH and temperature.Moreover,a novel in situ cross-linked hydrogel was prepared under physiological conditions,based on self-assembly of natural amino polysaccharide derivatives with homo-bifunctional PEG derivatives using Michael type addition,and the natural amino polysaccharide hydrogel also has some temperature sensitivity.The in vitro macromolecular drug delivery experiment suggested the favorable intelligent drug release abilities of these two gels,and they have potential to be novel intelligent drug delivery system.
Ⅰ.Preparation of gels
1.Preparation of glucosamine derivative microgel
Acrylic acid was attached to glucosamine via an amide bond between the carboxylic group and a free primary group.The microgels of the obtained functional glucosamine-AADG with NIPAM and AAc as the comonomer were prepared by the method of a free radical precipitation polymerization.
2.Preparation of natural amino polysaccharide hydrogel
Four homo-bifunctional PEG derivatives were synthesized:acrylate,bromoacetate, iodoacetate and maleimide functional PEG..And they were examined as cross-linking agents for thiol-modified derivatives of chitosan.The hydrogels were prepared by Michael type addition between the bifunctional PEG derivatives and thiol-modified chitosan.
Ⅱ.Characterization of gels
1.Size and morphology of microgel
The morphology of the resulting microgel was investigated by SEM.It is evident that microgels are well dispersed as individual particles with spherical shapes.It can be seen that the size of the microgels is around 50～60 nm in diameter in the solid state,and the microgels exhibit a narrow size distribution with an average diameter of around 100 nm in the wet state.
2.Pore size and morphology of hydrogel
The SEM images of freeze-dried hydrogels exhibited a highly macroporous spongelike structure and the average mesh size is about 10μm.After being dipped in PBS for 24 h and 7 d,the chains in the network degraded and the pores of the hydrogel increased
3.Thermal stability of hydrogel
All the hydrogels showed a two-stage thermal decomposition,the first-stage decomposition temperature was similar to that of chitosan,suggesting the introduction of PEG via Michael type addition did not decrease thermal stability of chitosan.And the weight loss results in the second-stage thermal decomposition were similar to the contents of PEG in hydrogels and indicate that the second-stage decomposition was caused by PEG.The second-stage degradation temperature increased when decreasing the content of PEG,which may be due to the inhibition of crystal growth of PEG caused by the stiff chitosan chain.
4.Rheology
The resulting of oscillatory stress sweep and frequency sweep indicated the higher mechanical strength and elasticity of hydrogel can be achieved by increasing the cross-linking density.
5.Swelling and degradation
All the hydrogels swelled rapidly and reached equilibrium within 0.5 h at 37℃, but within 4 h at 25℃.After reaching swelling equilibrium,all the hydrogels were rapidly degraded in the first 24 h,and then the degradation became slowly and hydrogels did not completely dissolve within six weeks.
Ⅲ.Intelligent drug release and biocompatibility of gels
1.Temperature sensitivity
The results of dynamic light scattering measurement show that the size of the microgels significantly increased with an increase in the temperature.And drug release profile represents the temperature sensitivity,under the same pH value,at 41℃,about 88%of drug was released within the initial 2 h;at 37℃,only about 79% of drug was released after 2 d.
The temperature sensitivity of hydrogel is also remarkable,the equilibrium swelling ratio of hydrogel at 25℃decreased to 25%of that at 37℃.For drug release profile,at 37℃,drug was completely released within 3 d;at 25℃,only about 60%of drug was released after 3 d.
2.pH sensitivity
When pH＜5.0,the diameters of microgels were nearly invariable regardless of the change of pH,and when pH≥5.0,the diameters became larger when the pH value was increased.And drug release profile represents the pH sensitivity,under the same temperature,at pH 6.9,about 88%of drug was released within the initial 2 h;at pH 7.4,about 79%drug was released within the initial 3 h.
3.Tissue-targeting
The drug release from microgel was two-stage under the tumor-surrounding environment,the initial burst release and subsequent slow release;and for the drug release under physiological conditions,the diffusing process was sustained slow and mild.Therefore,the release of drug at the tumor-surrounding environment is faster than that under normal physiological conditions.
The gelation time of hydrogel was determined by the thiols contents and concentration of CS-NAC,the terminal group type,molecular weight and the amount of cross-linking agents,and the reaction temperature.The controllability of hydrogel gelation time make macro form gel have tissue-targeting ability.
4.Biocompatibility
The cell viability study showed that the use of glucosamine may improve the biocompatibility of the microgels.The cell culture results illustrate that cells can migrate into the hydrogel networks and remain viable and maintain their 3D morphology during the 3 days culture.
The secondary structures of insulin and BSA as determined by CD spectra and SDS-PAGE were preserved in all gels.
Ⅵ.Mechanism of intelligent drug release
1.Shrinkage
The drug release from microgel has an initial burst,which was correlated to the NIPAM segment in the microgels.As the temperature increased up to a certain point, the water contained in the microgels was expelled due to the disruption of hydrogen bonding between water and the hydrophilic amide groups,then the hydrophobic isopropyl groups began to associate.And following the structural change and consequent enhanced surface hydrophobicity,the microgels shrunk and aggregated, the insulin was squeezed out.
2.Swelling
Fitted by semi-empirical mathematical model,mechanism of drug release from hydrogel was determined for Fick diffusion,and the release type was belong to swelling dominating drug release by further inference.Therefore,the crosslinking density determined the release rate of different hydrogels.
3.Degradation
Degradation of hydrogel did not have significant effect on drug release,which may be due to the huge difference between hydrodynamic diameter of BSA(d_h=7.2 nm) and hydrogel pore size(10μm).
引文
[1]高分子学会编。新版高分子辞典。日本尔京:朝倉書店,1988.
[2]林尚安,陆耘,梁兆熙。高分子化学。北京:科学出版社,2000,272.
[3]付献彩,沈文霞,姚天扬。物理化学(第四版)。北京:高等教育出版社,1995,1073.
[4]黑柳能光。高分子,1995,44:570.
[5]中尾浩,松田武久,西信元嗣,等。眼紀,1993,44:247、1107和1994,45:614.
[6]Tanaka T J.Collapse of Gels and the Critical Endpoint.Phys Rev Lett,1978,40:820-823.
[7]Rossi D De,Kajiwara K,Yamauchi A,et al.Polymer Gels,Plenum,1991.
[8]Gennes P G.Scaling Concepts in Polymer Physics.Comell U.P.Ithaca.N.Y.:1979.
[9]童真。高分子凝胶的体积相变。见:《现代科技综述大辞典》编委会编。现代科技综述大辞典,北京:北京出版社,1998,331.
[10]Murry M J,Snowden M J.The preparation,characterisation and applications of colloidal microgels.Adv Colloid Interface Sci,1995,54:73-91.
[11]Pelton R H.Temperature-sensitive aqueous microgels.Adv Colloid Interface Sci,2000,85:1-33.
[12]Ma X M,Cui Y J,Zhao X,et al.Different deswelling behavior of temperature-sensitive microgels of poly(N-isopropylacrylamide) crosslinked by polyethyleneglycol dimethacrylates.J Colloid Interface Sci,2004,276:53-59.
[13]Pelton R H,Richardson R,Cosgrove T,et al.The Effects of Temperature and Methanol Concentration on the Properties of Poly(N-isopropylacrylamide) at the Air/Solution Interface.Langmuir,2001,17:5118-5120.
[14]Wang G,Pelton R H,Zhang J.Sodium dodecyl sulfate binding to poly(N-isopropylacrylamide) microgel latex studied by isothermal titration calorimetry.Colloids Surf A:Physicochem Eng Asp,1999,153:335-340.
[15]Neradovic D,Soga O,Nostroum Van C F,et al.The effect of the processing and formulation parameters on the size of nanoparticles based on block copolymers of poly(ethylene glycol) and poly(N-isopropylacrylamide) with and without hydrolytically sensitive groups.Biomaterials,2004,25:2409-2418.
[16]John X,Pelton R.A new route to poly(N-isopropylacrylamide) microgels supporting a polyvinylamine corona.J Colloid Interface Sci,2004,276:113-117.
[17]Sayil C,Okay O.The effect of preparation temperature on the swelling behavior of poly (N-isopropylacrylamide) gels.Polymer Bulletin,2000,45:175-182.
[18]Saunders B R,Crowther H M,Morris E,et al.Factors affecting the swelling of poly(N-isopropylacrylamide) microgel particles:fundamental and commercial implications.Colloids Surf A:Physicochem Eng Asp,1999,149:57-64.
[19]Garcfa-Salinas M J,Romero-Cano M S,de las Nieves F J.Colloidal Stability of a Temperature-Sensitive Poly(N-isopropylacrylamide / 2-acrylamido-2-methylpropane sulphonic acid) Microgel. J Colloid Interface Sci, 2002, 248: 54-61.
[20] Senff H, Richtering W. Temperature sensitive microgel suspensions: Colloidal phase behavior and rheology of soft spheres. J Chem Phys, 1999, 111: 1705-1711.
[21] Fernandez-Nieves A, Vincent B, Delas-Nieves F J, et al. Charge Controlled Swelling of Microgel Particles. Macromolecules, 2000, 33: 2114-2118.
[22] Oshima H, Makino K, Fujimoto K. Electrophoretic Mobility of Latex Particles Covered with Temperature-Sensitive Hydrogel Layers. J Colloid Interface Sci, 1993, 159: 512-514.
[23] Richardson R M, Pelton R, Cosgrove T,et al. A Neutron Reflectivity Study of Poly(N-isopropylacrylamide) at the Air-Water Interface with and without Sodium Dodecyl Sulfate. Macromolecules, 2000, 33: 6269-6274.
[24] Todd H, Pelton R. Functional Group Distributions in Carboxylic Acid Containing Poly(N-isopropylacrylamide) Microgels. Langmuir, 2004, 20: 2123-2133.
[25] Abuin E, Leon a, Lissi E, et al. Binding of sodium dodecylsulfate to poly(N-isopropylacrylamide) microgels at different temperatures. Colloid Surf A: Physicochem Eng Asp, 1999, 147:55-65.
[26] Crowther H M, Vincent B. Swelling behavior of poly- N -isopropylacrylamide microgel particles in alcoholic solutions. Colloid Polym Sci, 1998, 276: 46-51.
[27] Zhu P W, Napper D H. Volume phase transitions of poly(N-isopropylacrylamide) latex particles in mixed water-N,N-dimethylformamide solutions. Chem Phys Lett, 1996, 256: 51-56.
[28] Zhu S Q, Chu B J. Synthesis and Volume Phase Transition of Poly(methacrylic acid-co-N-isopropylacrylamide) Microgel Particles in Water. J Phys Chem B, 1998, 102:1364-1371.
[29] Saunders B R, Vincent B. Microgel particles as model colloids: theory, properties and applications. Adv Colloid Interface Sci, 1999, 80: 1-25.
[30] Chan K, Pelton R, Zhang J. On the Formation of Colloidally Dispersed Phase-Separated Poly(N-isopropyiacrylamide). Langmuir, 1999, 15: 4018-4020.
[31] Snowden M J, Marston N J, Vincent B. The effect of surface modification on the stability characteristics of poly(N-isopropylacrylamide) latices under Brownian and flow conditions. Colloid Polym Sci, 1994, 272: 1273-1280.
[32] Napper D H. Steric stabilization. J Colloid Interface Sci, 1976, 58: 390-407.
[33] Weiss A, Hartenstein M, Dingenouts N,et al. Preparation and characterization of well-defined sterically stabilized latex particles with narrow size distribution. Colloid Polym Sci, 1998, 276: 794-799.
[34] Pelton R H, Pelton H M, Morphesis A, et al. Particle sizes and electrophoretic mobilities of poly(N-isopropylacrylamide) latex. Langmuir, 1989, 5: 816-818.
[35] Wu x, Pelton R H, Hamielec A E. The kinetics of poly(N-isopropylacrylamide) microgel latex formation. Colloid Polym Sci, 1994, 272: 467-477.
[36] Mcphee W, Tan K C, Pelton R H. Poly(N-isopropylacrylamide) Latices Prepared with Sodium Dodecyl Sulfate. J Colloid Interface Sci, 1993, 156: 24-30.
[37] Kiminta D M O, Luckham P F, Lenon S. The rheology of deformable and thermoresponsive microgel particles. Polymer, 1995, 36: 4827-4831.
[38] Kim J C, Kim J D. Release property of temperature-sensitive liposome containing poly(N-isopropylacrylamide). Colloids Surf B: Biointerface, 2002, 24: 45-52.
[39] Pelton R H, Chibante P. Preparation of aqueous latices with N-isopropylacrylamide. Colloids Surf, 1986,20:247-256.
[40] Shirota H, Endo N,Horie K. Volume phase transition of polymer gel in water and heavy water. Chem Phys, 1998, 238: 487-494.
[41] Gan D J, Lyon LA. Tunable Swelling Kinetics in Core-Shell Hydrogel Nanoparticles. J Am Chem Soc,2001,123: 7511-7517.
[42] Dowding D J, Vincent B, Williams E. Preparation and Swelling Properties of Poly(NIPAM) "Minigel" Particles Prepared by Inverse Suspension Polymerization. J Colloid Interface Sci, 2000, 221:268-272.
[43] Vo C D, Kuckling D, Alder H J P, et al. Preparation of thermosensitive nanogels by photo-cross-linking. Colloid Polym Sci, 2002, 280: 400-409.
[44] Zhou G, Elassari A, Delair T, et al. Synthesis and characterization of surface-cyanofunctionalized poly (N -isopropylacrylamide) latexes. Colloid Polym Sci, 1998, 276: 1131-1139.
[45] Duracher D, Sauzedde F, Ela ssari A, et al. Cationic amino-containing N -isopropyl- acrylamide-styrene copolymer latex particles: 1 -Particle size and morphology vs. polymerization process. Colloid Polym Sci, 1998, 276: 219-231.
[46] Kuckling D, Vo C D, Wohlrab S E, et al. Preparation of Nanogels with Temperature-Responsive Core and pH-Responsive Arms by Photo-Cross-Linking. Langmuir, 2002, 18:4263-4269.
[47] Hellweg T, Dewhurst C D, Bruckner S E, et al. Colloidal crystals made of poly( N -isopropylacrylamide) microgel particles. Colloid Polym Sci, 2000,278: 972-978.
[48] Zha L, Hu J, Wang C, et al. Preparation and characterization of poly ( N -isopropylacrylamide- co -dimethylaminoethyl methacrylate) microgel latexes. Colloid Polym Sci, 2002,280: 1-6.
[49] Greenwood R, Kendall K, Ritchie B,et al. The use of poly (N-isopropylacrylamide) microgels as a multi-functional processing aid for aqueous alumina suspensions. J European Ceramic Soc, 2000,20: 1707-1716.
[50] Sakuma S, Ishida Y, Akashi M, et al. Stabilization of salmon calcitonin by polystyrene nanoparticles having surface hydrophilic polymeric chains, against enzymatic degradation. Int J Pharm,1997,159: 181-189.
[52] Senff H, Richtering W. Influence of cross-link density on rheological properties of temperature-sensitive microgel suspensions. Colloid Polym Sci, 2000, 278: 830-840.
[53] Clinton D J, Lyon L A. Synthesis and Characterization of Multiresponsive Core-Shell Microgels.Macromolecules,2000,33:8301-8306.
[54]Kratz K,Hellweg T,Eimer W.Influence of charge density on the swelling of colloidal poly(N-isopropylacrylamide-co-acrylic acid) microgels.Colloids Surf A:Physicochem Eng Asp,2000,170:137-149.
[55]Hirose Y,Amiya T,Hirokawa Y,et al.Phase transition of submicron gel beads.Macromolecules,1987,20:1342-1344.
[56]Wu C.A comparison between the 'coil-to-globule' transition of linear chains and the "volume phase transition" of spherical microgels.Polymer,1998,39:4609-4619.
[57]Zhu P W,Napper D H.Coil-to-Globule Type Transitions and Swelling of Poly(N-isopropyl acrylamide) and Poly(acrylamide) at Latex Interfaces in Alcohol-Water Mixtures.J Colloid Interface Sci,1996,177:343-352.
[58]Zhang G E,Wu C.The Water/Methanol Complexation Induced Reentrant Coil-to-Globule-to-Coil Transition of Individual Homopolymer Chains in Extremely Dilute Solution.J Am Chem Soc,2001,123:1376-1380.
[59]Chan K,Pelton R H,Zhang J.On the Formation of Colloidally Dispersed Phase-Separated Poly(N-isopropylacrylamide).Langmuir,1999,15:4018-4020.
[60]Zhu P W,Napper D H.Entanglement Knotting in Globule-to-Coil Transitions of Poly(N-Isopropyacrylamide) at Interfaces.J Colloid Interface Sci,1994,168:380-385.
[61]周楠,周儒领,严晓虎,等.高分子单链微凝胶的合成与性质研究.河南大学学报(自然科学版),2001,31(4):48-50.
[62]Dowson K A,Gordov A V,Timoshenko E G,et al.Formation of mesoglobules from phase separation in dilute polymer solutions:a study in experiment,theory,and applications.Physica A,1997,244:68-80.
[63]Graham N B,Mao J W.Microgels Part 2.Solution polymerization using a urethane stepgrowth mechanism.Colloids Surf A:Physicochem Eng Asp,1996,118:211-220.
[64]Holtzscherer C,Candau F.Salt effect on solutions of nonionic surfactants and its influence on the stability of polymerized microemulsions.J Colloid Interface Sci,1988,125:97-110.
[65]Maryann B,Einarson T,John C.Electrosteric Stabilization of Colloidal Latex Dispersions.J Colloid Interface Sci,1993,155:165-172.
[66]Kratz K,Hellweg T,Eimer W.Structural changes in PNIPAM microgel particles as seen by SANS,DLS,and EM techniques.Polymer,2001,42:6631-6639.
[67]Crowther H M,Saundes B R,Mears M J,et al.Poly(NIPAM) microgel particle de-swelling:a light scattering and small-angle neutron scattering study.Colloids Surf A:Physicochem Eng Asp,1999,152:327-333.
[68]Kratz K,Lapp A,Eimer W,et al.Volume transition and structure of triethyleneglycol dimethacrylate,ethylenglykol dimethacrylate,and N,N'-methylene bis-acrylamide cross-linked poly(N-isopropyl acrylamide) microgels:a small angle neutron and dynamic light scattering study.Colloids Surf A:Physicochem Eng Asp,2002,197:55-67.
[69]Duracher D,Sauzedde F,Elaissari A,et al.Cationic amino-containing N-isopropyl- acrylamide-styrene copolymer particles:2-surface and colloidal characteristics.Colloid Polym Sci,1998,276:920-929.
[70]Duracher D,Elaissari A,Pichot C.Characterization of cross-linked poly(N -isopropylmethacrylamide) microgel latexes.Colloid Polym Sci,1999,277:905-913.
[71]Saunders B R,Crowther H M,Morries G E,et al.Factors affecting the swelling of poly(N-isopropylacrylamide) microgel particles:fundamental and commercial implications.Colloids Surf A:Physicochem Eng Asp,1999,149:57-64.
[72]Hatto N,Cosgrove T,Snowde M J.Novel microgel-particle colloids:the detailed characterisation of the layer structure and chain topology of silica:poly(NIPAM) core-shell particles.Polymer,2000,41:7133-7137.
[73]Yo Y D,Ch K S,Bae Y C.Phase transition of submicron sized N-alkylacryl amide-derivative copolymer particles:applicability of photon correlation spectroscopy.Polymer,1997,38:3471-3476.
[74]Mrikic J,Saunders B R.Microgel Particles as a Matrix for Polymerization:A Study of Poly(N-isopropylacrylamide)-Poly(N-methylpyrrole) Dispersions.J Colloid Interface Sci,2000,222:75-82.
[75]Mukac K,Sakurai M,Sawarnura S,et al.Swelling of poly(N-isopropylacrylamide) gels in water-alcohol(C1-C4) mixed solvents.J Phys Chem,1993,97:737-741.
[76]Woodword C N,Chowdhry B Z,Leharne S A,et al.The interaction of sodium dodecyl sulphate with colloidal microgel particles.Europ Polym,2000,36:1355-1364.
[77]陈洁,肖智成,熊波,等.用分光光度法研究温敏微凝胶的胶体稳定性.同济大学学报.2003,31(5):619-622.
[78]Indar P,Yasar Y.Internal dynamics in colloidal PNIPAM microgel particles immobilised in mesoscopic crystals.Colloids Surf A:Physicochem Eng Asp,2002,202:223-232.
[79]Agbugba C B,Hcndriksen B A,Chowdhry B Z,et al.The redispersibility and physico-chemieal properties of freeze-dried colloidal microgels.Colloids Surf A:Physicochem Eng Asp,1998,137:155-164.
[80]Garcia-Salinas M J,Rowero-Cano M S.Electrokinetic Characterization of Poly(N-isopropyl acrylamide) Mierogel Particles:Effect of Electrolyte Concentration and Temperature.J Colloid Interface Sci,2001,241:280-285.
[81]Ohshima H.Electrophoretic Mobility of Soft Particles.J Colloid Interface Sci,1994,163:474-483.
[82]Makino K,Kado H,Ohshima H.Aggregation behavior of poly(N-isopropylacrylamide)microspheres.Colloids Surf B:Biointerface,2001,20:347-353.
[83]Lin S Y,Chen K S,Chu L R.Drying methods affecting the particle sizes,phase transition,deswelling/reswelling processes and morphology of poly(N-isopropylacrylamide) microgel beads.Polymer,1999,40:6307-6312.
[84]Fang S J,Kawaguchi H.A thermosensitive amphoteric microsphere and its potential application as a biological carrier.Colloid Polym Sci,2002,280:984-989.
[85] Kawaguchi H, Fujimoto K, Mizuhara Y. Hydrogel microspheres III. Temperature- dependent adsorption of proteins on poly-N-isopropylacrylamide hydrogel microspheres. Colloid Polym Sci, 1992,270:53-57.
[86] Elaissari A, Burrel V. Thermosensitive magnetic latex particles for controlling protein adsorption and desorption. J Magn Magn Mater, 2000, 225: 151-155.
[87] Yashi M, Shiroya T, Fujimoto K, et al. Activity of enzymes immobilized on microspheres with thermosensitive hairs. Colloids Surf B: Biointerface, 1997, 8: 311-319.
[88] Shiroya T, Yashi M, Fujimoto K, et al. Control of enzymatic activity using thermosensitive polymers. Colloids Surf B: Biointerface, 1995,4: 275-285.
[89] Snowden M J, Thomas D, Vincent B. Use of colloidal microgels for the absorption of heavy metal and other ions from aqueous solution. Analyst, 1993, 118: 1367-1369.
[90] Morris G E, Vincent B, Snowden M J. Adsorption of Lead Ions ontoN-Isopropylacrylamide and Acrylic Acid Copolymer Microgels. J Colloid Interface Sci, 1997, 190: 198-205.
[91] Huang G, Gan D, Hu Z B, et al. Controlled drug release from hydrogel nanoparticle networks. J Control Release, 2004, 94: 303-311.
[92] Delair T, Murrier F, Elassari A, et al. Amino-containing cationic latex-oligodeoxy ribonucleotide conjugates: application to diagnostic test sensitivity enhancement. Colloids Surf A: Physicochem Eng Asp, 1999, 153: 341-353.
[93] Chois H, Yoon J J, Park T G. Galactosylated Poly(N-isopropylacrylamide) Hydrogel Submicrometer Particles for Specific Cellular Uptake within Hepatocytes. J Colloid Interface Sci, 2002,251:57-63.
[94] Elnas B, Owur M A, Senel S, et al. Thermosensitive N-isopropylacrylamide-vinylphenyl boronic acid copolymer latex particles for nucleotide isolation. Colloids Surf A: Physicochem Eng Asp, 2004, 232: 253-259.
[95] Ishii K. Synthesis of microgels and their application to coatings. Colloids Surf A: Physicochem Eng Asp, 1999, 153: 591-595.
[96] Das M, Mardyani S, Chan W, et al. Biofunctionalized pH-responsive microgels for cancer cell targeting: Rational design. Adv Mater, 2006, 18(1): 80-83.
[97] Zhang H-, -Mardyani S, Chan W C W, et al. Design of biocompatible chitosan microgels for targeted pH-mediated intracellular release of cancer therapeutics. Biomacromolecules, 2006, 7: 1568-1572.
[98] Wang C, Flynn N T, Langer R.. Controlled structure and properties of thermoresponsive nanoparticle-hydrogel composites. Adv Mater, 2004, 16(13): 1074-1079.
[99] Zhu M Q, Wang L Q, Exarhos G J, et al. Thermosensitive gold nanoparticles. J Am Chem Soc, 2004, 126(9): 2656-2657.
[100] Gorelikov I, Field L M, Kumacheva E. Hybrid microgels photoresponsive in the near-infrared spectral range. J Am Chem Soc, 2004, 126 (49): 15938-15939.
[101] Nikoobakht B, El-Sayed M A. Preparation and growth mechanism of gold nanorods (NRs) using seed-mediated growth method. Chem Mater, 2003, 15(10): 1957-1962.
[102]张侃,张黎明.环境敏感水凝胶的研究进展.广州化学,2001,26(4):46-54.
[103]何庆,盛京.响应性凝胶及其住约物控释上的应用.功能高分子学报,1997,10(1):118-127.
[104]罗宣干,王坦.N-异丙基丙烯酰胺系温度敏感聚合物和水凝胶的研究进展.化学通报,1996,(4):10-15.
[105]Feil H,Bae Y H,Feijen J,et al.Mutual influence of pH and temperature on the swelling of ionizable and thermosensitive hydrogels.Macromolecules,1992,25:5528-5530.
[106]陈延锋,伊敏.含甲基丙烯酸-N,N-二甲氨基乙酯水凝胶的紫外辐射合成及其性质研究.高分子学报,2001,(2):215-218.
[107]Sahoo S K,De T K,Ghosh P K,et al.pH-and thermo-sensitive hydrogel nanoparticles.J Colloid Interface Sci,1998,206:361-368.
[108]刘郁杨,范晓东,张双存.温度及pH敏感N-异丙基丙烯酰胺/β-环糊精水凝胶的合成与性能研究.高分子学报,2002,(5):618-622.
[109]刘鹏飞,彭静,吴季兰.辐射交联制备改性CMC水凝胶的溶胀行为研究.高分子学报,2002,(6):756-759.
[110]Chen G,Hoffman A S.Graft copolymers that exhibit temperature induced phase transitions over a wide range of pH.Nature,1995,373(5):49-52.
[111]Shah S,Dai W.Biodegradable pH/thermosensitive hydrogels for sustained delivery of biologically active agents.US:6451346.2002-9-17.
[112]高青雨,张玉娟.温度及pH敏感性水凝胶的合成及其性能研究.功能高分子学报,2001,14(2):158-161.
[113]高青雨,张玉娟,俞贤达.温度及pH敏感性N-乙烯基吡咯烷酮与丙烯酸β-一羟基丙酯共聚物/聚(丙烯酸)互穿网络水凝胶的合成及其性能研究.高分子学报,2001,(3):329-332.
[114]黄月文,罗宣干,卓仁禧.温度及pH值敏感水凝胶的合成和应用.广州化学,1996,(2):58-63.
[115]Beltran S,Baker J P,Hooper H H,et al.Swelling equilibria for weakly ionizable,temperature - sensitive hydrogels.Macromolecules,1991,24:549-551.
[116]Chen G,Hoffman A S.A new temperature- and pH-responsive copolymer for possible use in protein conjugation.Macromol Chem Phys,1995,190:1251-1259.
[117]Alvarez-Lorenzo C,Concheiro A.Reversible adsorption by a pH- and temperaturesensitive acrylic hydrogel.J Control Release,2002,80(123):247-257.
[118]刘晓华,唐黎明,戴,等.含聚氨酯型温度和pH双敏性水凝胶的合成及性能研究.高分子材料科学与工程,2003,19(1):49-52.
[119]Yuk S H,Cho S H,Lee S H.pH/temperature-Responsive polymer composed of poly((N,N-dimethylamino) ethylmethacylate-co-ethylacrylamide).Macromolecules,1997,30:6856-6859.
[120]卓仁禧,张先止.温度及pH敏感聚(丙烯酸)-CO-(丙烯腈)水凝胶的合成及性能研究.高分子学报,1998,(4):500-502.
[121]Maitra A N,Ghosh P K,Sahoo S K.pH and thermoresponsive hydrogel nanoparticles.Proc Int Symp Controlled Release Bioact Mater,1998,25th,234-235.
[122]陈双基,薛梅,李福绵.甲基丙烯酸-N,N-二甲氨基乙酯及其聚合物的热和pH响应性.高分子学报,1995,(3):373-375.
[123]Lim Y H,Kim D,Lee D S.Drug releasing characteristics of thenno- and pH-sensitive interpenetrating polymer networksbased on poly(N-isopropylacrylamide).J Appl Polym Sci,1997,64:2647-2655.
[124]Feil H,Bae Y H,Feijen J,et al.Mutual influence of pH and temperature on the swelling of ionizable and thermosensitive hydrogels.Macromolecules,1992,25:5528-5530.
[125]黄月文,罗宣干,卓仁禧.包埋在温度及pH值敏感水凝胶中的阿司匹林的控制释放研究.高分子材料科学与工程,1998,14(6):141-143.
[126]Kim E J,Cho S H,Yuk S H.Polymer microspheres composed of pH/temperature-sensitive polymer complex.Biomaterials,2001,22:2495-2499.
[127]刘锋,卓仁禧.温度及pH敏感水凝胶的合成及其在生物大分子控制释放中的应用.高分子材料科学与工程,1998,14(2):54-57.
[128]Ramkissoon-Ganorkar C,Liu F,Baudy,et al.Modulating insulin-release profile from pH/thermosensitive polymeric beads through polymer molecular weight.J Control Release,1999,59(3):287-298.
[1] Surendra N, Romila M, Ramesh C. Preparation, characterization and in vitro drug release studies of novel polymeric nanoparticles. Int J Pharm, 2006, 323: 146-152.
[2] John P D, Karl D H. The design and synthesis of immune regulatory vehicless: targets and approaches. Tetrahedron, 1989, 45: 4327-4369.
[3] Daniel C H, Lisa A F, Peter A P. SmI_2-Promoted deprotection of N-(arysulfonyl) glucosamines. J Org Chem 1997, 62: 4864-4866.
[4] Reginster J Y, Deroisy R. Long-term effects of glucosamine sulphate on osteoarthritis progression : a radomised , placebo-controlled clinical trial. The Lancet 2001, 357: 251-256.
[5] Zhang L, Liu W S, Han B Q, et al. Journal of Zhejiang University SCIENCE B, 2006, 7 (8): 608-615.
[6] Friedman S J, Skehan P. Membrane-active Drugs Potentiate the Killing of Tumor Cell by D-glucosamine. Proc Nat Acad Sci, 1980, 77 (2): 1172-1180.
[7] Ding H, Wu F, Zhang Z-r, et al. Synthesis and characterization of temperature-responsive copolymer of PELGA modified poly(N-isopropylacrylamide). Polymer, 2006, 47: 1575-1583.
[8] Chylinska J B, Urbanski T, Mordarski M. Dihydro-1,3-oxazine Derivatives and their Antitumor Activity. J Med Chem, 1963, 6: 484-487.
[9] Matsumura Y, Maeda H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins andthe antitumor vehicles smancs. Cancer Res, 1986, 46: 6387-6392.
[10] Davis S S, Ilium L. Polymeric microspheres as drug carriers. Biomaterials, 1988, 9: 111-115.
[11] Liu S Q, Tong Y W, Yang Y Y. Incorporation and in vitro release of doxorubicin in thermally sensitive micells made from poly(N-isopropylacrylamide-co-N,N-dimethyl- acrylamide)-b-poly(D,L-lactide-co-glycolide) with varying compositions. Biomaterials, 2005, 26: 5064-5074.
[12] Lee E S, Shin H J, Bae Y H, et al. Poly(L-histidine)-PEG block copolymer micelles and pH-induced destabilization. J Control Release, 2003, 90: 363-374.
[13] Lee E S, Na K, Bae YH. Polymeric micelle for tumor pH and folate-mediated targeting. J Control Release, 2003, 91: 103-113.
[14] Pollak A, Blumenfeld H, Whitesides G M, et al. Enzyme immobilization by condensation copolymerization into crosslinked polyacrylamide gels. J Am Chem Soc, 1980, 102: 6324-6336.
[15] D'Agosto F, Charreyre M T, Pichot C, et al. High Molecular Weight Hydrophilic Functional Copolymers by Free-Radical Copolymerization of Acrylamide and of N-Acryloylmorpholine with N-Acryloxysuccinimide: Application to the Synthesis of a Graft Copolymer. J Appl Polym Sci, 2003,88:1808-1816.
[16]Imoto T,Yagshito K.A Simple Activity Measurement of Lysozyme.Agr Biol Chem,1971,35:1154-1156.
[17]Pelton R.Temperature-sensitive aqueous microgels.Adv Colloid Interface Sci,2000,85:1-33.
[18]Bradford M M.A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.Anal Biochem,1976,72:248-254.
[19]Guggi D,Langoth N,Hoffer M H,et al.Comparative evaluation of cytotoxicity of a glucosamine-TBA conjugate and a chitosan-TBA conjugate.Int J Pharm,2004,278:353-360.
[20]D'Agosto F,Charreyre M T,Pichot C,et al.Kinetic Study of Free-Radical Solution Copolymerization of N-Acryloylmorpholine with an Activated Ester-Type Monomer,N-Acryloxysuccinimide.Macromol Chem Phys,2001,202:1689-1699.
[21]Myung-G B,Rene R.Relative Lectin Binding Properties of T-Antigen-Containing Glycopolymers:Copolymerization of N-Acryloylated T-Antigen Monomer vs.Graft Conjugation of Aminated T-Antigen Ligands onto Poly(N-acryloxysuccinimide).Macromol Biosci,2001,1:305-311.
[22]Gupta A K,Madan S,Maitra A,et al.Ketorolac entrapped in polymeric micelles:preparation,characterisation and ocular anti-inflammatory studies.Int J Pharm,2000,209:1-14.
[23]Lin C L,Chiu W Y,Lee C F.Preparation,morphology,and thermoresponsive properties of poly(N-isopropylacrylamide)-based copolymer microgels.J Polym Sci Part A:Polym Chem,2006,44:356-370.
[24]Wu Y,Guo J,Yang W.Preparation and characterization of chitosan-poly(acrylic acid)polymer magnetic microspheres.Polymer,2006,47:5287-5294.
[25]Kim H K,Park TG.Synthesis and characterization of thermally reversible bioconjugates composed of α-chymotrypsin and poly(N-isopropylacrylamide-co-acrylamido-2-deoxy-D -glucose).Enzyme Microb Technol,1998,25:31-40.
[26]Park T G,Hoffman AS.Sodium chloride-induced phase transition in nonionic poly(N-isopropylacrylamide) gel.Macromolecules,1993,26:5045-5048.
[27]Mikael R,Alex R,Brian V.Flocculation of microgel particles with sodium chloride and sodium polystyrene sulfonate as a function of temperature.Langmuir,2004,20:3536-3542.
[28]Kratz K,Hellweg T,Eimer W.Influence of charge density on the swelling of colloidal poly (N-isopropylacrylamide-co-acrylic acid) microgel.Colloids Surf A:Physicochem Eng Aspects,2000,170:137-149.
[29]Costa P,Lobo J M S.Modeling and comparison of dissolution profiles.Eur J Pharm Sci,2001,13:123-133.
[30]Zhu G Z,Mallery S R,Schwendeman S P.Stabilization of proteins encapsulated in injectable poly(lactide-co-glycolide).Nat Biotechnol,2000,18:52-57
[31]Yin L C,Ding J Y,Fei L K,et al.Beneficial properties for insulin absorption using superporous hydrogel containing interpenetrating polymer network as oral delivery vehicles.Int J Pharm,2008,350:220-229
[32]Das M,Mardyani S,Kumacheva E,et al.Biofunctionalized pH-Responsive Microgels for Cancer Cell Targeting:Rational Design.Adv Mater,2006,18:80-83.
[1] Hoffman A S. Hydrogels for biomedical applications. Adv Drug Delivery Rev, 2002, 43: 3-12.
[2] Peppas N A, Hilt J Z, Langer R, et al. Hydrogels in Biology and Medicine: From Molecular Principles to Bionanotechnology. Adv Mater, 2006, 18: 1345-1360.
[3] Hoare T R, Kohane D S. Hydrogels in drug delivery: Progress and challenges. Polymer, 2008, 49: 1993-2007.
[4] Lee K Y, Mooney D J. Hydrogels for Tissue Engineering. Chem Rev, 2001, 101 (7): 1869-1879.
[5] Nuttelman C R, Rice M A, Anseth K S, et al. Macromolecular monomers for the synthesis of hydrogel niches and their application in cell encapsulation and tissue engineering. Prog Polym Sci, 2008,33: 167-179.
[6] Hatefi A, Amsden B. Biodegradable injectable in situ forming drug delivery systems. J Control Release 2002, 80: 9-28.
[7] Packhaeuser C B, Schnieders J, Kissel T, et al. In situ forming parenteral drug delivery systems: an overview. Eur J Pharm Biopharm, 2004, 58: 445-455.
[8] Kretlow J D, Klouda L, Mikos A G. Injectable matrices and scaffolds for drug delivery in tissue engineering. Adv Drug Delivery Rev, 2007, 59: 263-273.
[9] Van Tomme S R, Storm G, Hennink W E. In situ gelling hydrogels for pharmaceutical and biomedical applications. Int J Pharm, 2008, 355: 1-18.
[10] He C L, Kim S W, Lee D S. In situ gelling stimuli-sensitive block copolymer hydrogels for drug delivery. J Control Release, 2008, 127: 189-207.
[11] Sawhney A S, Pathak C P, Hubbell J A. Bioerodible hydrogels based on photopolymerized poly(ethylene glycol)-co-poly(alpha-hydroxy acid) diacrylate macromers. Macromolecules, 1993, 26: 581-587.
[12] Mi E-L, Shyu S S, Lu K T, et al. Chitosan-polyelectrolyte complexation for the preparation of gel beads and controlled release of anticancer drug. II. Effect of pH-dependent ionic crosslinking or interpolymer complex using tripolyphosphate or polyphosphate as reagent. J Appl Polym Sci, 1999,74: 1093-1107.
[13] Kuo C K, Ma P X. Ionically crosslinked alginate hydrogels as scaffolds for tissue engineering. Part 1. Structure, gelation rate and mechanical properties. Biomaterials, 2001, 22: 511-521.
[14] Van Tomme S R, van Steenbergen M J, Hennink W E, et al. Self-gelling hydrogels based on oppositely charged dextran microspheres. Biomaterials, 2005, 26: 2129-2135.
[15] Huang X, Lowe T L. Biodegradable thermoresponsive hydrogels for aqueous encapsulation and controlled release of hydrophilic model drugs. Biomacromolecules, 2005, 6: 2131~2139.
[16] Haines-Butterick L, Rajagopal K, Schneider J P, et al. Controlling hydrogelation kinetics by peptide design for three-dimensional encapsulation and injectable delivery of cells. Proc Nat Acad Sci USA, 2007, 104: 7791-7796.
[17] Choi H S, Yui N. Design of rapidly assembling supramolecular systems responsive to synchronized stimuli. Prog Polym Sci, 2006, 31: 121-144.
[18] Qiu B, Stefanos S, Stein S, et al. A hydrogel prepared by in situ cross-linking of a thiolcontaining poly(ethylene glycol)-based copolymer: a new biomaterial for protein drug delivery. Biomaterials, 2003, 24: 11-18.
[19] Tae G, Kim Y J, Hoffman A S. Formation of a novel heparin-based hydrogel in the presence of heparinbinding biomolecules. Biomacromolecules, 2007, 8: 1979-1986.
[20] Shu X. Z.; Liu Y.; Prestwich G. D. In situ crosslinkable hyaluronan hydrogels for tissue engineering. Biomaterials, 2004, 25: 1339-1348.
[21] Krauland A, Leitner V M, Bernkop-Schniirch A. Improvement in the In Situ Gelling Properties of Deacetylated Gellan Gum by the Immobilization of Thiol Groups. J Pharm Sci, 2003,92: 1234-1241.
[22] Ongoka P, Mauze B E. Synthese regiospecifique d'amido-1 vinyl-2 cyclopropanes a partir de lithiens allyliques monohalogenes et d'amides tertiaires a-ethyleniques. J Org Chem, 1987, 322: 131-139.
[23] Elbert D L, Hubbell J A. Conjugate Addition Reactions Combined with Free-Radical Cross-Linking for the Design of Materials for Tissue Engineering. Biomacromolecules, 2001, 2: 430-441.
[24] Cruise G M, Scharp D S, Hubbell J A. Characterization of permeability and network structure of interfacially photopolymerized polyethylene glycol) diacrylate hydrogels. Biomaterials, 1998, 19: 1287-1294.
[25] Chen Y Y, Baker G L. Synthesis and Properties of ABA amphiphiles. J Org Chem, 1999, 64: 6870-6873.
[26] Huh K M, Ooya T, Lee W K, et al. Supramolecular Structured Hydrogels Showing a Reversible Phase Transition by Inclusion Complexation between Poly(ethylene glycol) Grafted Dextran and α-Cyclodextrin. Macromolecules, 2001, 34: 8657-8662.
[27] Kalgutkar A. S.; Crews B. C; Marnett L. J. Design, synthesis, and biochemical evaluation of N-substituted maleimides as inhibitors of prostaglandin endoperoxide synthases. J Med Chem, 1996,39: 1692-1703.
[28] Liu X.-h.; Wang H.-k.; Prestwich, G. D. Photopatterning of antibodies on biosensors. Bioconjugate Chem, 2000, 11: 755-761.
[29] Jeong B, Bae Y H, Kim S W. Thermoreversible Gelation of PEG-PLGA-PEG Triblock Copolymer Aqueous Solutions. Macromolecules, 1999, 32: 7064-7069.
[30] Fangkangwanwong J, Akashi M, Kida T, et al. One-pot synthesis in aqueous system for water-soluble chitosan-graft-poly(ethylene glycol) methyl ether. Biopolymers, 2006, 82:580-586.
[31] Ghosh K, Shu X Z, Prestwich G D. Rheological Characterization of in Situ Cross-Linkable Hyaluronan Hydrogels. Biomacromolecules, 2005, 6: 2857-2865.
[32] Hiemstra C, Zhong Z, Feijen J. Novel in Situ Forming, Degradable Dextran Hydrogels by Michael Addition Chemistry: Synthesis, Rheology, and Degradation. Macromolecules, 2007, 40: 1165-1173.
[33] Hiemstra C, Zhong Z, Feijen J. Rapidly in Situ-Forming Degradable Hydrogels from Dextran Thiols through Michael Addition. Biomacromolecules, 2007, 8: 1548-1556.
[34] Hermanson, G. T. 2.2 Maleimides. In Bioconjugate Techniques; Academic Press: San Diego, CA, 1996. 148-150.
[35] Casadei M A, Pitarresi G, Calabrese R. Biodegradable and pH-Sensitive Hydrogels for Potential Colon-Specific Drug Delivery: Characterization and In Vitro Release Studies. Biomacromolecules, 2008, 9(1): 43-49.
[36] Vanderhooft J L, Mann B K, Prestwich G D. Synthesis and Characterization of Novel Thiol-Reactive Poly(ethylene glycol) Cross-Linkers for Extracellular-Matrix-Mimetic Biomaterials. Biomacromolecules, 2007, 8 (9): 2883-2889.
[1] Metters A, Hubbell J A. Network Formation and Degradation Behavior of Hydrogels Formed by Michael-Type Addition Reactions. Biomacromolecules, 2005, 6: 290~301.
[2] Metters A T, Schoenmakers R G, Hubbell J A, et al. Poly(ethylene glycol) hydrogels formed by conjugate addition with controllable swelling, degradation, and release of pharmaceutically active proteins. J Control Release, 2005, 102: 619-627.
[3] Rizzi S C, Hubbell J. A. Recombinant Protein-co-PEG Networks as Cell-Adhesive and Proteolytically Degradable Hydrogel Matrixes. Part I: Development and Physicochemical Characteristics. Biomacromolecules, 2005, 6: 1226-1238.
[4] Shu X Z, Ghosh K, Prestwich G D, et al. Attachment and spreading of fibroblasts on an RGD peptide-modified injectable hyaluronan hydrogel. J Biomed Mater Res, 2004, 68A: 365-375.
[5] Ghosh K, Shu X Z, Prestwich G D, et al. Rheological Characterization of in Situ Cross-Linkable Hyaluronan Hydrogels. Biomacromolecules, 2005; 6: 2857-2865.
[6] Shu X Z, Liu Y C, Prestwich G D. Synthesis and evaluation of injectable, in situ crosslinkable synthetic extracellular matrices for tissue engineering. J Biomed Mater Res, 2006; 79A: 902-912.
[7] Hiemstra C, Zhong Z, Feijen J, et al. Novel in Situ Forming, Degradable Dextran Hydrogels by Michael Addition Chemistry: Synthesis, Rheology, and Degradation. Macromolecules, 2007; 40: 1165-1173.
[8] Hiemstra C, Zhong Z, Feijen J, et al. Rapidly in Situ-Forming Degradable Hydrogels from Dextran Thiols through Michael Addition. Biomacromolecules, 2007; 8: 1548-1556.
[9] Hiemstra C, Hennink W E, Feijen J, et al. Release of model proteins and basic fibroblast growth factor from in situ forming degradable dextran hydrogels J Control Release, 2007; 122: 71-78.
[10] Ravi Kumar M N V, Muzzarelli R A A, Domb A J, et al. Chitosan Chemistry and Pharmaceutical Perspectives. Chem Rev, 2004, 104: 6017-6084.
[11] Sashiwa H, Aiba S. Chemically modified chitin and chitosan as biomaterials. Prog Polym Sci, 2004, 29: 887-908.
[12] Rinaudo M. Chitin and chitosan: Properties and applications. Prog Polym Sci, 2006, 31: 603-632.
[13] Gingras M, Paradis I, Berthod F. Nerve regeneration in a collagen-chitosan tissue-engineered skin transplanted on nude mice. Biomaterials, 2003, 24: 1653-1661.
[14] Wang Y C, Lin M C, Hsieh H J, et al. Fabrication of a novel porous PGA-chitosan hybrid matrix for tissue engineering. Biomaterials, 2003, 24: 1047-1057.
[15] Francis Suh J K, Matthew H W T. Application of chitosan-based polysaccharide biomaterials in cartilage tissue engineering: a review. Biomaterials, 2000, 21: 2589-2598.
[16] Bhattarai N, Ramay H R, Zhang M Q, et al. PEG-grafted chitosan as an injectable thermosensitive hydrogel for sustained protein release . J Control Release, 2005, 103: 609-624.
[17] Bhattarai N, Matsen F A, Zhang M Q. PEG-Grafted Chitosan as an Injectable Thermoreversible Hydrogel. Macromol Biosci, 2005, 5: 107-111.
[18] Wua J, Wei W, Ma G H, et al. A thermosensitive hydrogel based on quaternized chitosan and poly(ethylene glycol) for nasal drug delivery system. Biomaterials, 2007, 28: 2220-2232.
[19] Kim M S, Noh I, Tae G, et al. Synthesis and characterization of in situ chitosan - based hydrogel via grafting of carboxyethyl acrylate. J Biomed Mater Res, 2007, 83A: 674-684.
[20] Shu X Z, Liu Y C, Prestwich G D, et al. Disulfide Cross-Linked Hyaluronan Hydrogels. Biomacromolecules, 2002, 3: 1304-1311.
[21] Zhao W, Yu L, Sun J, et al. The compatibility and morphology of chitosan-poly (ethylene oxide) blends. J Macromol Sci Phys, 1995, B34(3): 231-235.
[22] Nieto J M, Peniche-Covas C, Padron G. Characterization of chitosan by pyrolysis-mass spectrometry, thermal analysis and differential scanning calorimetry. Thermochim Acta, 1991, 176,63-68.
[23] Kiuchi H, Kai W, Inoue Y. Preparation and Characterization of Poly(ethylene glycol) Crosslinked Chitosan Films. J Appl Polym Sci, 2008, 107: 3823-3830.
[24] Anseth K S, Bowman C N, Brannon-Peppas L. Mechanical properties of hydrogels and their experimental determination. Biomaterials, 1996, 17: 1647-1657.
[25] Santovena A, Alvarez-Lorenzo C, Farina J B, et al. Rheological properties of PLGA film-based implants: correlation with polymer degradation and SPf66 antimalaric synthetic peptide release. Biomaterials, 2004,25: 925-931.
[26] Lee K Y, Bouhadir K H, Mooney D J. Controlled degradation of hydrogels using multi-functional cross-linking molecules. Biomaterials, 2004,25: 2461-2466.
[27] Kavanagh G M, Ross-Murphy S B. Rheological characterisation of polymer gels. Prog Polym Sci, 1998, 23: 533-562.
[28] Lutolf M P, Hubbell J A. Synthesis and Physicochemical Characterization of End-Linked Poly (ethylene glycol)-co-peptide Hydrogels Formed by Michael-Type Addition. Biomacromolecules, 2003,4: 713-722.
[29] Elbert D L; Hubbell J A. Conjugate addition reactions combined with free-radical cross-linking for the design of materials for tissue engineering. Biomacromolecules, 2001, 2:430-441.
[30] El-Sherbiny I M, Abdel-Bary E M, Harding D R K. Swelling Characteristics and In Vitro Drug Release Study with pH- and Thermally Sensitive Hydrogels Based on Modified Chitosan. J Appl Polym Sci, 2006, 102: 977-985.
[31] Khurma J R, Nand A V. Temperature and pH sensitive hydrogels composed of chitosan and poly(ethylene glycol). Polym Bull, 2008, 59: 805-812.
[32] Kim S J, Park S J, Kim S I. Swelling behavior of interpenetrating polymer network hydrogels composed of poly(vinyl alcohol) and chitosan. React Funct Polym, 2003, 55: 53-59.
[33] Costa P, Lobo J M S. Modeling and comparison of dissolution profiles. Eur J Pharm Sci, 2001,13:123-133.
[34]Korsmeyer R W,Gurny R,Peppas N A,et al.Mechanism of solute release from porous hydrophilic polymers.Int J Pharm,1983,15:25-35.
[35]Peppas N A.Analysis of Fickian and non-Fickian drug release from polymers.Pharm Acta Helv,1985,60:110-111.
[36]Sagara K,Kim S W.A new synthesis of galactose-poly(ethylene glycol)-polyethylenimine for gene delivery to hepatocytes.J Control Release,2002,79:271-281.
[37]顾雪蓉,朱育平。凝胶化学。北京:化学工业出版社,2005,128-137.
[38]Hiemstra C,Zhong Z Y,Feijen J,et al.Release of model proteins and basic fibroblast growth factor from in situ forming degradable dextran hydrogels.J Control Release,2007,122:71-78.
[39]Yin L C,Ding J Y,Fei L K,et al.Beneficial properties for insulin absorption using superporous hydrogel containing interpenetrating polymer network as oral delivery vehicles.Int J Pharm,2008,350:220-229
[40]Kim B S,Mooney D J.Development of biocompatible synthetic extracellular matrices for tissue engineering.Trends in Biotech,1998,16:224-225.
[41]Langer R S,Vacanti J P.Tissue Engineering.Science,1993,260:920-926.
[42]Underhill G H,Chen A A,Bhatia S N,et al.Assessment of hepatocellular function within PEG hydrogels.Biomaterials,2007,28:256-270.
[2]林尚安,陆耘,梁兆熙。高分子化学。北京:科学出版社,2000,272.
[3]付献彩,沈文霞,姚天扬。物理化学(第四版)。北京:高等教育出版社,1995,1073.
[4]黑柳能光。高分子,1995,44:570.
[5]中尾浩,松田武久,西信元嗣,等。眼紀,1993,44:247、1107和1994,45:614.
[6]Tanaka T J.Collapse of Gels and the Critical Endpoint.Phys Rev Lett,1978,40:820-823.
[7]Rossi D De,Kajiwara K,Yamauchi A,et al.Polymer Gels,Plenum,1991.
[8]Gennes P G.Scaling Concepts in Polymer Physics.Comell U.P.Ithaca.N.Y.:1979.
[9]童真。高分子凝胶的体积相变。见:《现代科技综述大辞典》编委会编。现代科技综述大辞典,北京:北京出版社,1998,331.
[10]Murry M J,Snowden M J.The preparation,characterisation and applications of colloidal microgels.Adv Colloid Interface Sci,1995,54:73-91.
[11]Pelton R H.Temperature-sensitive aqueous microgels.Adv Colloid Interface Sci,2000,85:1-33.
[12]Ma X M,Cui Y J,Zhao X,et al.Different deswelling behavior of temperature-sensitive microgels of poly(N-isopropylacrylamide) crosslinked by polyethyleneglycol dimethacrylates.J Colloid Interface Sci,2004,276:53-59.
[13]Pelton R H,Richardson R,Cosgrove T,et al.The Effects of Temperature and Methanol Concentration on the Properties of Poly(N-isopropylacrylamide) at the Air/Solution Interface.Langmuir,2001,17:5118-5120.
[14]Wang G,Pelton R H,Zhang J.Sodium dodecyl sulfate binding to poly(N-isopropylacrylamide) microgel latex studied by isothermal titration calorimetry.Colloids Surf A:Physicochem Eng Asp,1999,153:335-340.
[15]Neradovic D,Soga O,Nostroum Van C F,et al.The effect of the processing and formulation parameters on the size of nanoparticles based on block copolymers of poly(ethylene glycol) and poly(N-isopropylacrylamide) with and without hydrolytically sensitive groups.Biomaterials,2004,25:2409-2418.
[16]John X,Pelton R.A new route to poly(N-isopropylacrylamide) microgels supporting a polyvinylamine corona.J Colloid Interface Sci,2004,276:113-117.
[17]Sayil C,Okay O.The effect of preparation temperature on the swelling behavior of poly (N-isopropylacrylamide) gels.Polymer Bulletin,2000,45:175-182.
[18]Saunders B R,Crowther H M,Morris E,et al.Factors affecting the swelling of poly(N-isopropylacrylamide) microgel particles:fundamental and commercial implications.Colloids Surf A:Physicochem Eng Asp,1999,149:57-64.
[19]Garcfa-Salinas M J,Romero-Cano M S,de las Nieves F J.Colloidal Stability of a Temperature-Sensitive Poly(N-isopropylacrylamide / 2-acrylamido-2-methylpropane sulphonic acid) Microgel. J Colloid Interface Sci, 2002, 248: 54-61.
[20] Senff H, Richtering W. Temperature sensitive microgel suspensions: Colloidal phase behavior and rheology of soft spheres. J Chem Phys, 1999, 111: 1705-1711.
[21] Fernandez-Nieves A, Vincent B, Delas-Nieves F J, et al. Charge Controlled Swelling of Microgel Particles. Macromolecules, 2000, 33: 2114-2118.
[22] Oshima H, Makino K, Fujimoto K. Electrophoretic Mobility of Latex Particles Covered with Temperature-Sensitive Hydrogel Layers. J Colloid Interface Sci, 1993, 159: 512-514.
[23] Richardson R M, Pelton R, Cosgrove T,et al. A Neutron Reflectivity Study of Poly(N-isopropylacrylamide) at the Air-Water Interface with and without Sodium Dodecyl Sulfate. Macromolecules, 2000, 33: 6269-6274.
[24] Todd H, Pelton R. Functional Group Distributions in Carboxylic Acid Containing Poly(N-isopropylacrylamide) Microgels. Langmuir, 2004, 20: 2123-2133.
[25] Abuin E, Leon a, Lissi E, et al. Binding of sodium dodecylsulfate to poly(N-isopropylacrylamide) microgels at different temperatures. Colloid Surf A: Physicochem Eng Asp, 1999, 147:55-65.
[26] Crowther H M, Vincent B. Swelling behavior of poly- N -isopropylacrylamide microgel particles in alcoholic solutions. Colloid Polym Sci, 1998, 276: 46-51.
[27] Zhu P W, Napper D H. Volume phase transitions of poly(N-isopropylacrylamide) latex particles in mixed water-N,N-dimethylformamide solutions. Chem Phys Lett, 1996, 256: 51-56.
[28] Zhu S Q, Chu B J. Synthesis and Volume Phase Transition of Poly(methacrylic acid-co-N-isopropylacrylamide) Microgel Particles in Water. J Phys Chem B, 1998, 102:1364-1371.
[29] Saunders B R, Vincent B. Microgel particles as model colloids: theory, properties and applications. Adv Colloid Interface Sci, 1999, 80: 1-25.
[30] Chan K, Pelton R, Zhang J. On the Formation of Colloidally Dispersed Phase-Separated Poly(N-isopropyiacrylamide). Langmuir, 1999, 15: 4018-4020.
[31] Snowden M J, Marston N J, Vincent B. The effect of surface modification on the stability characteristics of poly(N-isopropylacrylamide) latices under Brownian and flow conditions. Colloid Polym Sci, 1994, 272: 1273-1280.
[32] Napper D H. Steric stabilization. J Colloid Interface Sci, 1976, 58: 390-407.
[33] Weiss A, Hartenstein M, Dingenouts N,et al. Preparation and characterization of well-defined sterically stabilized latex particles with narrow size distribution. Colloid Polym Sci, 1998, 276: 794-799.
[34] Pelton R H, Pelton H M, Morphesis A, et al. Particle sizes and electrophoretic mobilities of poly(N-isopropylacrylamide) latex. Langmuir, 1989, 5: 816-818.
[35] Wu x, Pelton R H, Hamielec A E. The kinetics of poly(N-isopropylacrylamide) microgel latex formation. Colloid Polym Sci, 1994, 272: 467-477.
[36] Mcphee W, Tan K C, Pelton R H. Poly(N-isopropylacrylamide) Latices Prepared with Sodium Dodecyl Sulfate. J Colloid Interface Sci, 1993, 156: 24-30.
[37] Kiminta D M O, Luckham P F, Lenon S. The rheology of deformable and thermoresponsive microgel particles. Polymer, 1995, 36: 4827-4831.
[38] Kim J C, Kim J D. Release property of temperature-sensitive liposome containing poly(N-isopropylacrylamide). Colloids Surf B: Biointerface, 2002, 24: 45-52.
[39] Pelton R H, Chibante P. Preparation of aqueous latices with N-isopropylacrylamide. Colloids Surf, 1986,20:247-256.
[40] Shirota H, Endo N,Horie K. Volume phase transition of polymer gel in water and heavy water. Chem Phys, 1998, 238: 487-494.
[41] Gan D J, Lyon LA. Tunable Swelling Kinetics in Core-Shell Hydrogel Nanoparticles. J Am Chem Soc,2001,123: 7511-7517.
[42] Dowding D J, Vincent B, Williams E. Preparation and Swelling Properties of Poly(NIPAM) "Minigel" Particles Prepared by Inverse Suspension Polymerization. J Colloid Interface Sci, 2000, 221:268-272.
[43] Vo C D, Kuckling D, Alder H J P, et al. Preparation of thermosensitive nanogels by photo-cross-linking. Colloid Polym Sci, 2002, 280: 400-409.
[44] Zhou G, Elassari A, Delair T, et al. Synthesis and characterization of surface-cyanofunctionalized poly (N -isopropylacrylamide) latexes. Colloid Polym Sci, 1998, 276: 1131-1139.
[45] Duracher D, Sauzedde F, Ela ssari A, et al. Cationic amino-containing N -isopropyl- acrylamide-styrene copolymer latex particles: 1 -Particle size and morphology vs. polymerization process. Colloid Polym Sci, 1998, 276: 219-231.
[46] Kuckling D, Vo C D, Wohlrab S E, et al. Preparation of Nanogels with Temperature-Responsive Core and pH-Responsive Arms by Photo-Cross-Linking. Langmuir, 2002, 18:4263-4269.
[47] Hellweg T, Dewhurst C D, Bruckner S E, et al. Colloidal crystals made of poly( N -isopropylacrylamide) microgel particles. Colloid Polym Sci, 2000,278: 972-978.
[48] Zha L, Hu J, Wang C, et al. Preparation and characterization of poly ( N -isopropylacrylamide- co -dimethylaminoethyl methacrylate) microgel latexes. Colloid Polym Sci, 2002,280: 1-6.
[49] Greenwood R, Kendall K, Ritchie B,et al. The use of poly (N-isopropylacrylamide) microgels as a multi-functional processing aid for aqueous alumina suspensions. J European Ceramic Soc, 2000,20: 1707-1716.
[50] Sakuma S, Ishida Y, Akashi M, et al. Stabilization of salmon calcitonin by polystyrene nanoparticles having surface hydrophilic polymeric chains, against enzymatic degradation. Int J Pharm,1997,159: 181-189.
[52] Senff H, Richtering W. Influence of cross-link density on rheological properties of temperature-sensitive microgel suspensions. Colloid Polym Sci, 2000, 278: 830-840.
[53] Clinton D J, Lyon L A. Synthesis and Characterization of Multiresponsive Core-Shell Microgels.Macromolecules,2000,33:8301-8306.
[54]Kratz K,Hellweg T,Eimer W.Influence of charge density on the swelling of colloidal poly(N-isopropylacrylamide-co-acrylic acid) microgels.Colloids Surf A:Physicochem Eng Asp,2000,170:137-149.
[55]Hirose Y,Amiya T,Hirokawa Y,et al.Phase transition of submicron gel beads.Macromolecules,1987,20:1342-1344.
[56]Wu C.A comparison between the 'coil-to-globule' transition of linear chains and the "volume phase transition" of spherical microgels.Polymer,1998,39:4609-4619.
[57]Zhu P W,Napper D H.Coil-to-Globule Type Transitions and Swelling of Poly(N-isopropyl acrylamide) and Poly(acrylamide) at Latex Interfaces in Alcohol-Water Mixtures.J Colloid Interface Sci,1996,177:343-352.
[58]Zhang G E,Wu C.The Water/Methanol Complexation Induced Reentrant Coil-to-Globule-to-Coil Transition of Individual Homopolymer Chains in Extremely Dilute Solution.J Am Chem Soc,2001,123:1376-1380.
[59]Chan K,Pelton R H,Zhang J.On the Formation of Colloidally Dispersed Phase-Separated Poly(N-isopropylacrylamide).Langmuir,1999,15:4018-4020.
[60]Zhu P W,Napper D H.Entanglement Knotting in Globule-to-Coil Transitions of Poly(N-Isopropyacrylamide) at Interfaces.J Colloid Interface Sci,1994,168:380-385.
[61]周楠,周儒领,严晓虎,等.高分子单链微凝胶的合成与性质研究.河南大学学报(自然科学版),2001,31(4):48-50.
[62]Dowson K A,Gordov A V,Timoshenko E G,et al.Formation of mesoglobules from phase separation in dilute polymer solutions:a study in experiment,theory,and applications.Physica A,1997,244:68-80.
[63]Graham N B,Mao J W.Microgels Part 2.Solution polymerization using a urethane stepgrowth mechanism.Colloids Surf A:Physicochem Eng Asp,1996,118:211-220.
[64]Holtzscherer C,Candau F.Salt effect on solutions of nonionic surfactants and its influence on the stability of polymerized microemulsions.J Colloid Interface Sci,1988,125:97-110.
[65]Maryann B,Einarson T,John C.Electrosteric Stabilization of Colloidal Latex Dispersions.J Colloid Interface Sci,1993,155:165-172.
[66]Kratz K,Hellweg T,Eimer W.Structural changes in PNIPAM microgel particles as seen by SANS,DLS,and EM techniques.Polymer,2001,42:6631-6639.
[67]Crowther H M,Saundes B R,Mears M J,et al.Poly(NIPAM) microgel particle de-swelling:a light scattering and small-angle neutron scattering study.Colloids Surf A:Physicochem Eng Asp,1999,152:327-333.
[68]Kratz K,Lapp A,Eimer W,et al.Volume transition and structure of triethyleneglycol dimethacrylate,ethylenglykol dimethacrylate,and N,N'-methylene bis-acrylamide cross-linked poly(N-isopropyl acrylamide) microgels:a small angle neutron and dynamic light scattering study.Colloids Surf A:Physicochem Eng Asp,2002,197:55-67.
[69]Duracher D,Sauzedde F,Elaissari A,et al.Cationic amino-containing N-isopropyl- acrylamide-styrene copolymer particles:2-surface and colloidal characteristics.Colloid Polym Sci,1998,276:920-929.
[70]Duracher D,Elaissari A,Pichot C.Characterization of cross-linked poly(N -isopropylmethacrylamide) microgel latexes.Colloid Polym Sci,1999,277:905-913.
[71]Saunders B R,Crowther H M,Morries G E,et al.Factors affecting the swelling of poly(N-isopropylacrylamide) microgel particles:fundamental and commercial implications.Colloids Surf A:Physicochem Eng Asp,1999,149:57-64.
[72]Hatto N,Cosgrove T,Snowde M J.Novel microgel-particle colloids:the detailed characterisation of the layer structure and chain topology of silica:poly(NIPAM) core-shell particles.Polymer,2000,41:7133-7137.
[73]Yo Y D,Ch K S,Bae Y C.Phase transition of submicron sized N-alkylacryl amide-derivative copolymer particles:applicability of photon correlation spectroscopy.Polymer,1997,38:3471-3476.
[74]Mrikic J,Saunders B R.Microgel Particles as a Matrix for Polymerization:A Study of Poly(N-isopropylacrylamide)-Poly(N-methylpyrrole) Dispersions.J Colloid Interface Sci,2000,222:75-82.
[75]Mukac K,Sakurai M,Sawarnura S,et al.Swelling of poly(N-isopropylacrylamide) gels in water-alcohol(C1-C4) mixed solvents.J Phys Chem,1993,97:737-741.
[76]Woodword C N,Chowdhry B Z,Leharne S A,et al.The interaction of sodium dodecyl sulphate with colloidal microgel particles.Europ Polym,2000,36:1355-1364.
[77]陈洁,肖智成,熊波,等.用分光光度法研究温敏微凝胶的胶体稳定性.同济大学学报.2003,31(5):619-622.
[78]Indar P,Yasar Y.Internal dynamics in colloidal PNIPAM microgel particles immobilised in mesoscopic crystals.Colloids Surf A:Physicochem Eng Asp,2002,202:223-232.
[79]Agbugba C B,Hcndriksen B A,Chowdhry B Z,et al.The redispersibility and physico-chemieal properties of freeze-dried colloidal microgels.Colloids Surf A:Physicochem Eng Asp,1998,137:155-164.
[80]Garcia-Salinas M J,Rowero-Cano M S.Electrokinetic Characterization of Poly(N-isopropyl acrylamide) Mierogel Particles:Effect of Electrolyte Concentration and Temperature.J Colloid Interface Sci,2001,241:280-285.
[81]Ohshima H.Electrophoretic Mobility of Soft Particles.J Colloid Interface Sci,1994,163:474-483.
[82]Makino K,Kado H,Ohshima H.Aggregation behavior of poly(N-isopropylacrylamide)microspheres.Colloids Surf B:Biointerface,2001,20:347-353.
[83]Lin S Y,Chen K S,Chu L R.Drying methods affecting the particle sizes,phase transition,deswelling/reswelling processes and morphology of poly(N-isopropylacrylamide) microgel beads.Polymer,1999,40:6307-6312.
[84]Fang S J,Kawaguchi H.A thermosensitive amphoteric microsphere and its potential application as a biological carrier.Colloid Polym Sci,2002,280:984-989.
[85] Kawaguchi H, Fujimoto K, Mizuhara Y. Hydrogel microspheres III. Temperature- dependent adsorption of proteins on poly-N-isopropylacrylamide hydrogel microspheres. Colloid Polym Sci, 1992,270:53-57.
[86] Elaissari A, Burrel V. Thermosensitive magnetic latex particles for controlling protein adsorption and desorption. J Magn Magn Mater, 2000, 225: 151-155.
[87] Yashi M, Shiroya T, Fujimoto K, et al. Activity of enzymes immobilized on microspheres with thermosensitive hairs. Colloids Surf B: Biointerface, 1997, 8: 311-319.
[88] Shiroya T, Yashi M, Fujimoto K, et al. Control of enzymatic activity using thermosensitive polymers. Colloids Surf B: Biointerface, 1995,4: 275-285.
[89] Snowden M J, Thomas D, Vincent B. Use of colloidal microgels for the absorption of heavy metal and other ions from aqueous solution. Analyst, 1993, 118: 1367-1369.
[90] Morris G E, Vincent B, Snowden M J. Adsorption of Lead Ions ontoN-Isopropylacrylamide and Acrylic Acid Copolymer Microgels. J Colloid Interface Sci, 1997, 190: 198-205.
[91] Huang G, Gan D, Hu Z B, et al. Controlled drug release from hydrogel nanoparticle networks. J Control Release, 2004, 94: 303-311.
[92] Delair T, Murrier F, Elassari A, et al. Amino-containing cationic latex-oligodeoxy ribonucleotide conjugates: application to diagnostic test sensitivity enhancement. Colloids Surf A: Physicochem Eng Asp, 1999, 153: 341-353.
[93] Chois H, Yoon J J, Park T G. Galactosylated Poly(N-isopropylacrylamide) Hydrogel Submicrometer Particles for Specific Cellular Uptake within Hepatocytes. J Colloid Interface Sci, 2002,251:57-63.
[94] Elnas B, Owur M A, Senel S, et al. Thermosensitive N-isopropylacrylamide-vinylphenyl boronic acid copolymer latex particles for nucleotide isolation. Colloids Surf A: Physicochem Eng Asp, 2004, 232: 253-259.
[95] Ishii K. Synthesis of microgels and their application to coatings. Colloids Surf A: Physicochem Eng Asp, 1999, 153: 591-595.
[96] Das M, Mardyani S, Chan W, et al. Biofunctionalized pH-responsive microgels for cancer cell targeting: Rational design. Adv Mater, 2006, 18(1): 80-83.
[97] Zhang H-, -Mardyani S, Chan W C W, et al. Design of biocompatible chitosan microgels for targeted pH-mediated intracellular release of cancer therapeutics. Biomacromolecules, 2006, 7: 1568-1572.
[98] Wang C, Flynn N T, Langer R.. Controlled structure and properties of thermoresponsive nanoparticle-hydrogel composites. Adv Mater, 2004, 16(13): 1074-1079.
[99] Zhu M Q, Wang L Q, Exarhos G J, et al. Thermosensitive gold nanoparticles. J Am Chem Soc, 2004, 126(9): 2656-2657.
[100] Gorelikov I, Field L M, Kumacheva E. Hybrid microgels photoresponsive in the near-infrared spectral range. J Am Chem Soc, 2004, 126 (49): 15938-15939.
[101] Nikoobakht B, El-Sayed M A. Preparation and growth mechanism of gold nanorods (NRs) using seed-mediated growth method. Chem Mater, 2003, 15(10): 1957-1962.
[102]张侃,张黎明.环境敏感水凝胶的研究进展.广州化学,2001,26(4):46-54.
[103]何庆,盛京.响应性凝胶及其住约物控释上的应用.功能高分子学报,1997,10(1):118-127.
[104]罗宣干,王坦.N-异丙基丙烯酰胺系温度敏感聚合物和水凝胶的研究进展.化学通报,1996,(4):10-15.
[105]Feil H,Bae Y H,Feijen J,et al.Mutual influence of pH and temperature on the swelling of ionizable and thermosensitive hydrogels.Macromolecules,1992,25:5528-5530.
[106]陈延锋,伊敏.含甲基丙烯酸-N,N-二甲氨基乙酯水凝胶的紫外辐射合成及其性质研究.高分子学报,2001,(2):215-218.
[107]Sahoo S K,De T K,Ghosh P K,et al.pH-and thermo-sensitive hydrogel nanoparticles.J Colloid Interface Sci,1998,206:361-368.
[108]刘郁杨,范晓东,张双存.温度及pH敏感N-异丙基丙烯酰胺/β-环糊精水凝胶的合成与性能研究.高分子学报,2002,(5):618-622.
[109]刘鹏飞,彭静,吴季兰.辐射交联制备改性CMC水凝胶的溶胀行为研究.高分子学报,2002,(6):756-759.
[110]Chen G,Hoffman A S.Graft copolymers that exhibit temperature induced phase transitions over a wide range of pH.Nature,1995,373(5):49-52.
[111]Shah S,Dai W.Biodegradable pH/thermosensitive hydrogels for sustained delivery of biologically active agents.US:6451346.2002-9-17.
[112]高青雨,张玉娟.温度及pH敏感性水凝胶的合成及其性能研究.功能高分子学报,2001,14(2):158-161.
[113]高青雨,张玉娟,俞贤达.温度及pH敏感性N-乙烯基吡咯烷酮与丙烯酸β-一羟基丙酯共聚物/聚(丙烯酸)互穿网络水凝胶的合成及其性能研究.高分子学报,2001,(3):329-332.
[114]黄月文,罗宣干,卓仁禧.温度及pH值敏感水凝胶的合成和应用.广州化学,1996,(2):58-63.
[115]Beltran S,Baker J P,Hooper H H,et al.Swelling equilibria for weakly ionizable,temperature - sensitive hydrogels.Macromolecules,1991,24:549-551.
[116]Chen G,Hoffman A S.A new temperature- and pH-responsive copolymer for possible use in protein conjugation.Macromol Chem Phys,1995,190:1251-1259.
[117]Alvarez-Lorenzo C,Concheiro A.Reversible adsorption by a pH- and temperaturesensitive acrylic hydrogel.J Control Release,2002,80(123):247-257.
[118]刘晓华,唐黎明,戴,等.含聚氨酯型温度和pH双敏性水凝胶的合成及性能研究.高分子材料科学与工程,2003,19(1):49-52.
[119]Yuk S H,Cho S H,Lee S H.pH/temperature-Responsive polymer composed of poly((N,N-dimethylamino) ethylmethacylate-co-ethylacrylamide).Macromolecules,1997,30:6856-6859.
[120]卓仁禧,张先止.温度及pH敏感聚(丙烯酸)-CO-(丙烯腈)水凝胶的合成及性能研究.高分子学报,1998,(4):500-502.
[121]Maitra A N,Ghosh P K,Sahoo S K.pH and thermoresponsive hydrogel nanoparticles.Proc Int Symp Controlled Release Bioact Mater,1998,25th,234-235.
[122]陈双基,薛梅,李福绵.甲基丙烯酸-N,N-二甲氨基乙酯及其聚合物的热和pH响应性.高分子学报,1995,(3):373-375.
[123]Lim Y H,Kim D,Lee D S.Drug releasing characteristics of thenno- and pH-sensitive interpenetrating polymer networksbased on poly(N-isopropylacrylamide).J Appl Polym Sci,1997,64:2647-2655.
[124]Feil H,Bae Y H,Feijen J,et al.Mutual influence of pH and temperature on the swelling of ionizable and thermosensitive hydrogels.Macromolecules,1992,25:5528-5530.
[125]黄月文,罗宣干,卓仁禧.包埋在温度及pH值敏感水凝胶中的阿司匹林的控制释放研究.高分子材料科学与工程,1998,14(6):141-143.
[126]Kim E J,Cho S H,Yuk S H.Polymer microspheres composed of pH/temperature-sensitive polymer complex.Biomaterials,2001,22:2495-2499.
[127]刘锋,卓仁禧.温度及pH敏感水凝胶的合成及其在生物大分子控制释放中的应用.高分子材料科学与工程,1998,14(2):54-57.
[128]Ramkissoon-Ganorkar C,Liu F,Baudy,et al.Modulating insulin-release profile from pH/thermosensitive polymeric beads through polymer molecular weight.J Control Release,1999,59(3):287-298.
[1] Surendra N, Romila M, Ramesh C. Preparation, characterization and in vitro drug release studies of novel polymeric nanoparticles. Int J Pharm, 2006, 323: 146-152.
[2] John P D, Karl D H. The design and synthesis of immune regulatory vehicless: targets and approaches. Tetrahedron, 1989, 45: 4327-4369.
[3] Daniel C H, Lisa A F, Peter A P. SmI_2-Promoted deprotection of N-(arysulfonyl) glucosamines. J Org Chem 1997, 62: 4864-4866.
[4] Reginster J Y, Deroisy R. Long-term effects of glucosamine sulphate on osteoarthritis progression : a radomised , placebo-controlled clinical trial. The Lancet 2001, 357: 251-256.
[5] Zhang L, Liu W S, Han B Q, et al. Journal of Zhejiang University SCIENCE B, 2006, 7 (8): 608-615.
[6] Friedman S J, Skehan P. Membrane-active Drugs Potentiate the Killing of Tumor Cell by D-glucosamine. Proc Nat Acad Sci, 1980, 77 (2): 1172-1180.
[7] Ding H, Wu F, Zhang Z-r, et al. Synthesis and characterization of temperature-responsive copolymer of PELGA modified poly(N-isopropylacrylamide). Polymer, 2006, 47: 1575-1583.
[8] Chylinska J B, Urbanski T, Mordarski M. Dihydro-1,3-oxazine Derivatives and their Antitumor Activity. J Med Chem, 1963, 6: 484-487.
[9] Matsumura Y, Maeda H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins andthe antitumor vehicles smancs. Cancer Res, 1986, 46: 6387-6392.
[10] Davis S S, Ilium L. Polymeric microspheres as drug carriers. Biomaterials, 1988, 9: 111-115.
[11] Liu S Q, Tong Y W, Yang Y Y. Incorporation and in vitro release of doxorubicin in thermally sensitive micells made from poly(N-isopropylacrylamide-co-N,N-dimethyl- acrylamide)-b-poly(D,L-lactide-co-glycolide) with varying compositions. Biomaterials, 2005, 26: 5064-5074.
[12] Lee E S, Shin H J, Bae Y H, et al. Poly(L-histidine)-PEG block copolymer micelles and pH-induced destabilization. J Control Release, 2003, 90: 363-374.
[13] Lee E S, Na K, Bae YH. Polymeric micelle for tumor pH and folate-mediated targeting. J Control Release, 2003, 91: 103-113.
[14] Pollak A, Blumenfeld H, Whitesides G M, et al. Enzyme immobilization by condensation copolymerization into crosslinked polyacrylamide gels. J Am Chem Soc, 1980, 102: 6324-6336.
[15] D'Agosto F, Charreyre M T, Pichot C, et al. High Molecular Weight Hydrophilic Functional Copolymers by Free-Radical Copolymerization of Acrylamide and of N-Acryloylmorpholine with N-Acryloxysuccinimide: Application to the Synthesis of a Graft Copolymer. J Appl Polym Sci, 2003,88:1808-1816.
[16]Imoto T,Yagshito K.A Simple Activity Measurement of Lysozyme.Agr Biol Chem,1971,35:1154-1156.
[17]Pelton R.Temperature-sensitive aqueous microgels.Adv Colloid Interface Sci,2000,85:1-33.
[18]Bradford M M.A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.Anal Biochem,1976,72:248-254.
[19]Guggi D,Langoth N,Hoffer M H,et al.Comparative evaluation of cytotoxicity of a glucosamine-TBA conjugate and a chitosan-TBA conjugate.Int J Pharm,2004,278:353-360.
[20]D'Agosto F,Charreyre M T,Pichot C,et al.Kinetic Study of Free-Radical Solution Copolymerization of N-Acryloylmorpholine with an Activated Ester-Type Monomer,N-Acryloxysuccinimide.Macromol Chem Phys,2001,202:1689-1699.
[21]Myung-G B,Rene R.Relative Lectin Binding Properties of T-Antigen-Containing Glycopolymers:Copolymerization of N-Acryloylated T-Antigen Monomer vs.Graft Conjugation of Aminated T-Antigen Ligands onto Poly(N-acryloxysuccinimide).Macromol Biosci,2001,1:305-311.
[22]Gupta A K,Madan S,Maitra A,et al.Ketorolac entrapped in polymeric micelles:preparation,characterisation and ocular anti-inflammatory studies.Int J Pharm,2000,209:1-14.
[23]Lin C L,Chiu W Y,Lee C F.Preparation,morphology,and thermoresponsive properties of poly(N-isopropylacrylamide)-based copolymer microgels.J Polym Sci Part A:Polym Chem,2006,44:356-370.
[24]Wu Y,Guo J,Yang W.Preparation and characterization of chitosan-poly(acrylic acid)polymer magnetic microspheres.Polymer,2006,47:5287-5294.
[25]Kim H K,Park TG.Synthesis and characterization of thermally reversible bioconjugates composed of α-chymotrypsin and poly(N-isopropylacrylamide-co-acrylamido-2-deoxy-D -glucose).Enzyme Microb Technol,1998,25:31-40.
[26]Park T G,Hoffman AS.Sodium chloride-induced phase transition in nonionic poly(N-isopropylacrylamide) gel.Macromolecules,1993,26:5045-5048.
[27]Mikael R,Alex R,Brian V.Flocculation of microgel particles with sodium chloride and sodium polystyrene sulfonate as a function of temperature.Langmuir,2004,20:3536-3542.
[28]Kratz K,Hellweg T,Eimer W.Influence of charge density on the swelling of colloidal poly (N-isopropylacrylamide-co-acrylic acid) microgel.Colloids Surf A:Physicochem Eng Aspects,2000,170:137-149.
[29]Costa P,Lobo J M S.Modeling and comparison of dissolution profiles.Eur J Pharm Sci,2001,13:123-133.
[30]Zhu G Z,Mallery S R,Schwendeman S P.Stabilization of proteins encapsulated in injectable poly(lactide-co-glycolide).Nat Biotechnol,2000,18:52-57
[31]Yin L C,Ding J Y,Fei L K,et al.Beneficial properties for insulin absorption using superporous hydrogel containing interpenetrating polymer network as oral delivery vehicles.Int J Pharm,2008,350:220-229
[32]Das M,Mardyani S,Kumacheva E,et al.Biofunctionalized pH-Responsive Microgels for Cancer Cell Targeting:Rational Design.Adv Mater,2006,18:80-83.
[1] Hoffman A S. Hydrogels for biomedical applications. Adv Drug Delivery Rev, 2002, 43: 3-12.
[2] Peppas N A, Hilt J Z, Langer R, et al. Hydrogels in Biology and Medicine: From Molecular Principles to Bionanotechnology. Adv Mater, 2006, 18: 1345-1360.
[3] Hoare T R, Kohane D S. Hydrogels in drug delivery: Progress and challenges. Polymer, 2008, 49: 1993-2007.
[4] Lee K Y, Mooney D J. Hydrogels for Tissue Engineering. Chem Rev, 2001, 101 (7): 1869-1879.
[5] Nuttelman C R, Rice M A, Anseth K S, et al. Macromolecular monomers for the synthesis of hydrogel niches and their application in cell encapsulation and tissue engineering. Prog Polym Sci, 2008,33: 167-179.
[6] Hatefi A, Amsden B. Biodegradable injectable in situ forming drug delivery systems. J Control Release 2002, 80: 9-28.
[7] Packhaeuser C B, Schnieders J, Kissel T, et al. In situ forming parenteral drug delivery systems: an overview. Eur J Pharm Biopharm, 2004, 58: 445-455.
[8] Kretlow J D, Klouda L, Mikos A G. Injectable matrices and scaffolds for drug delivery in tissue engineering. Adv Drug Delivery Rev, 2007, 59: 263-273.
[9] Van Tomme S R, Storm G, Hennink W E. In situ gelling hydrogels for pharmaceutical and biomedical applications. Int J Pharm, 2008, 355: 1-18.
[10] He C L, Kim S W, Lee D S. In situ gelling stimuli-sensitive block copolymer hydrogels for drug delivery. J Control Release, 2008, 127: 189-207.
[11] Sawhney A S, Pathak C P, Hubbell J A. Bioerodible hydrogels based on photopolymerized poly(ethylene glycol)-co-poly(alpha-hydroxy acid) diacrylate macromers. Macromolecules, 1993, 26: 581-587.
[12] Mi E-L, Shyu S S, Lu K T, et al. Chitosan-polyelectrolyte complexation for the preparation of gel beads and controlled release of anticancer drug. II. Effect of pH-dependent ionic crosslinking or interpolymer complex using tripolyphosphate or polyphosphate as reagent. J Appl Polym Sci, 1999,74: 1093-1107.
[13] Kuo C K, Ma P X. Ionically crosslinked alginate hydrogels as scaffolds for tissue engineering. Part 1. Structure, gelation rate and mechanical properties. Biomaterials, 2001, 22: 511-521.
[14] Van Tomme S R, van Steenbergen M J, Hennink W E, et al. Self-gelling hydrogels based on oppositely charged dextran microspheres. Biomaterials, 2005, 26: 2129-2135.
[15] Huang X, Lowe T L. Biodegradable thermoresponsive hydrogels for aqueous encapsulation and controlled release of hydrophilic model drugs. Biomacromolecules, 2005, 6: 2131~2139.
[16] Haines-Butterick L, Rajagopal K, Schneider J P, et al. Controlling hydrogelation kinetics by peptide design for three-dimensional encapsulation and injectable delivery of cells. Proc Nat Acad Sci USA, 2007, 104: 7791-7796.
[17] Choi H S, Yui N. Design of rapidly assembling supramolecular systems responsive to synchronized stimuli. Prog Polym Sci, 2006, 31: 121-144.
[18] Qiu B, Stefanos S, Stein S, et al. A hydrogel prepared by in situ cross-linking of a thiolcontaining poly(ethylene glycol)-based copolymer: a new biomaterial for protein drug delivery. Biomaterials, 2003, 24: 11-18.
[19] Tae G, Kim Y J, Hoffman A S. Formation of a novel heparin-based hydrogel in the presence of heparinbinding biomolecules. Biomacromolecules, 2007, 8: 1979-1986.
[20] Shu X. Z.; Liu Y.; Prestwich G. D. In situ crosslinkable hyaluronan hydrogels for tissue engineering. Biomaterials, 2004, 25: 1339-1348.
[21] Krauland A, Leitner V M, Bernkop-Schniirch A. Improvement in the In Situ Gelling Properties of Deacetylated Gellan Gum by the Immobilization of Thiol Groups. J Pharm Sci, 2003,92: 1234-1241.
[22] Ongoka P, Mauze B E. Synthese regiospecifique d'amido-1 vinyl-2 cyclopropanes a partir de lithiens allyliques monohalogenes et d'amides tertiaires a-ethyleniques. J Org Chem, 1987, 322: 131-139.
[23] Elbert D L, Hubbell J A. Conjugate Addition Reactions Combined with Free-Radical Cross-Linking for the Design of Materials for Tissue Engineering. Biomacromolecules, 2001, 2: 430-441.
[24] Cruise G M, Scharp D S, Hubbell J A. Characterization of permeability and network structure of interfacially photopolymerized polyethylene glycol) diacrylate hydrogels. Biomaterials, 1998, 19: 1287-1294.
[25] Chen Y Y, Baker G L. Synthesis and Properties of ABA amphiphiles. J Org Chem, 1999, 64: 6870-6873.
[26] Huh K M, Ooya T, Lee W K, et al. Supramolecular Structured Hydrogels Showing a Reversible Phase Transition by Inclusion Complexation between Poly(ethylene glycol) Grafted Dextran and α-Cyclodextrin. Macromolecules, 2001, 34: 8657-8662.
[27] Kalgutkar A. S.; Crews B. C; Marnett L. J. Design, synthesis, and biochemical evaluation of N-substituted maleimides as inhibitors of prostaglandin endoperoxide synthases. J Med Chem, 1996,39: 1692-1703.
[28] Liu X.-h.; Wang H.-k.; Prestwich, G. D. Photopatterning of antibodies on biosensors. Bioconjugate Chem, 2000, 11: 755-761.
[29] Jeong B, Bae Y H, Kim S W. Thermoreversible Gelation of PEG-PLGA-PEG Triblock Copolymer Aqueous Solutions. Macromolecules, 1999, 32: 7064-7069.
[30] Fangkangwanwong J, Akashi M, Kida T, et al. One-pot synthesis in aqueous system for water-soluble chitosan-graft-poly(ethylene glycol) methyl ether. Biopolymers, 2006, 82:580-586.
[31] Ghosh K, Shu X Z, Prestwich G D. Rheological Characterization of in Situ Cross-Linkable Hyaluronan Hydrogels. Biomacromolecules, 2005, 6: 2857-2865.
[32] Hiemstra C, Zhong Z, Feijen J. Novel in Situ Forming, Degradable Dextran Hydrogels by Michael Addition Chemistry: Synthesis, Rheology, and Degradation. Macromolecules, 2007, 40: 1165-1173.
[33] Hiemstra C, Zhong Z, Feijen J. Rapidly in Situ-Forming Degradable Hydrogels from Dextran Thiols through Michael Addition. Biomacromolecules, 2007, 8: 1548-1556.
[34] Hermanson, G. T. 2.2 Maleimides. In Bioconjugate Techniques; Academic Press: San Diego, CA, 1996. 148-150.
[35] Casadei M A, Pitarresi G, Calabrese R. Biodegradable and pH-Sensitive Hydrogels for Potential Colon-Specific Drug Delivery: Characterization and In Vitro Release Studies. Biomacromolecules, 2008, 9(1): 43-49.
[36] Vanderhooft J L, Mann B K, Prestwich G D. Synthesis and Characterization of Novel Thiol-Reactive Poly(ethylene glycol) Cross-Linkers for Extracellular-Matrix-Mimetic Biomaterials. Biomacromolecules, 2007, 8 (9): 2883-2889.
[1] Metters A, Hubbell J A. Network Formation and Degradation Behavior of Hydrogels Formed by Michael-Type Addition Reactions. Biomacromolecules, 2005, 6: 290~301.
[2] Metters A T, Schoenmakers R G, Hubbell J A, et al. Poly(ethylene glycol) hydrogels formed by conjugate addition with controllable swelling, degradation, and release of pharmaceutically active proteins. J Control Release, 2005, 102: 619-627.
[3] Rizzi S C, Hubbell J. A. Recombinant Protein-co-PEG Networks as Cell-Adhesive and Proteolytically Degradable Hydrogel Matrixes. Part I: Development and Physicochemical Characteristics. Biomacromolecules, 2005, 6: 1226-1238.
[4] Shu X Z, Ghosh K, Prestwich G D, et al. Attachment and spreading of fibroblasts on an RGD peptide-modified injectable hyaluronan hydrogel. J Biomed Mater Res, 2004, 68A: 365-375.
[5] Ghosh K, Shu X Z, Prestwich G D, et al. Rheological Characterization of in Situ Cross-Linkable Hyaluronan Hydrogels. Biomacromolecules, 2005; 6: 2857-2865.
[6] Shu X Z, Liu Y C, Prestwich G D. Synthesis and evaluation of injectable, in situ crosslinkable synthetic extracellular matrices for tissue engineering. J Biomed Mater Res, 2006; 79A: 902-912.
[7] Hiemstra C, Zhong Z, Feijen J, et al. Novel in Situ Forming, Degradable Dextran Hydrogels by Michael Addition Chemistry: Synthesis, Rheology, and Degradation. Macromolecules, 2007; 40: 1165-1173.
[8] Hiemstra C, Zhong Z, Feijen J, et al. Rapidly in Situ-Forming Degradable Hydrogels from Dextran Thiols through Michael Addition. Biomacromolecules, 2007; 8: 1548-1556.
[9] Hiemstra C, Hennink W E, Feijen J, et al. Release of model proteins and basic fibroblast growth factor from in situ forming degradable dextran hydrogels J Control Release, 2007; 122: 71-78.
[10] Ravi Kumar M N V, Muzzarelli R A A, Domb A J, et al. Chitosan Chemistry and Pharmaceutical Perspectives. Chem Rev, 2004, 104: 6017-6084.
[11] Sashiwa H, Aiba S. Chemically modified chitin and chitosan as biomaterials. Prog Polym Sci, 2004, 29: 887-908.
[12] Rinaudo M. Chitin and chitosan: Properties and applications. Prog Polym Sci, 2006, 31: 603-632.
[13] Gingras M, Paradis I, Berthod F. Nerve regeneration in a collagen-chitosan tissue-engineered skin transplanted on nude mice. Biomaterials, 2003, 24: 1653-1661.
[14] Wang Y C, Lin M C, Hsieh H J, et al. Fabrication of a novel porous PGA-chitosan hybrid matrix for tissue engineering. Biomaterials, 2003, 24: 1047-1057.
[15] Francis Suh J K, Matthew H W T. Application of chitosan-based polysaccharide biomaterials in cartilage tissue engineering: a review. Biomaterials, 2000, 21: 2589-2598.
[16] Bhattarai N, Ramay H R, Zhang M Q, et al. PEG-grafted chitosan as an injectable thermosensitive hydrogel for sustained protein release . J Control Release, 2005, 103: 609-624.
[17] Bhattarai N, Matsen F A, Zhang M Q. PEG-Grafted Chitosan as an Injectable Thermoreversible Hydrogel. Macromol Biosci, 2005, 5: 107-111.
[18] Wua J, Wei W, Ma G H, et al. A thermosensitive hydrogel based on quaternized chitosan and poly(ethylene glycol) for nasal drug delivery system. Biomaterials, 2007, 28: 2220-2232.
[19] Kim M S, Noh I, Tae G, et al. Synthesis and characterization of in situ chitosan - based hydrogel via grafting of carboxyethyl acrylate. J Biomed Mater Res, 2007, 83A: 674-684.
[20] Shu X Z, Liu Y C, Prestwich G D, et al. Disulfide Cross-Linked Hyaluronan Hydrogels. Biomacromolecules, 2002, 3: 1304-1311.
[21] Zhao W, Yu L, Sun J, et al. The compatibility and morphology of chitosan-poly (ethylene oxide) blends. J Macromol Sci Phys, 1995, B34(3): 231-235.
[22] Nieto J M, Peniche-Covas C, Padron G. Characterization of chitosan by pyrolysis-mass spectrometry, thermal analysis and differential scanning calorimetry. Thermochim Acta, 1991, 176,63-68.
[23] Kiuchi H, Kai W, Inoue Y. Preparation and Characterization of Poly(ethylene glycol) Crosslinked Chitosan Films. J Appl Polym Sci, 2008, 107: 3823-3830.
[24] Anseth K S, Bowman C N, Brannon-Peppas L. Mechanical properties of hydrogels and their experimental determination. Biomaterials, 1996, 17: 1647-1657.
[25] Santovena A, Alvarez-Lorenzo C, Farina J B, et al. Rheological properties of PLGA film-based implants: correlation with polymer degradation and SPf66 antimalaric synthetic peptide release. Biomaterials, 2004,25: 925-931.
[26] Lee K Y, Bouhadir K H, Mooney D J. Controlled degradation of hydrogels using multi-functional cross-linking molecules. Biomaterials, 2004,25: 2461-2466.
[27] Kavanagh G M, Ross-Murphy S B. Rheological characterisation of polymer gels. Prog Polym Sci, 1998, 23: 533-562.
[28] Lutolf M P, Hubbell J A. Synthesis and Physicochemical Characterization of End-Linked Poly (ethylene glycol)-co-peptide Hydrogels Formed by Michael-Type Addition. Biomacromolecules, 2003,4: 713-722.
[29] Elbert D L; Hubbell J A. Conjugate addition reactions combined with free-radical cross-linking for the design of materials for tissue engineering. Biomacromolecules, 2001, 2:430-441.
[30] El-Sherbiny I M, Abdel-Bary E M, Harding D R K. Swelling Characteristics and In Vitro Drug Release Study with pH- and Thermally Sensitive Hydrogels Based on Modified Chitosan. J Appl Polym Sci, 2006, 102: 977-985.
[31] Khurma J R, Nand A V. Temperature and pH sensitive hydrogels composed of chitosan and poly(ethylene glycol). Polym Bull, 2008, 59: 805-812.
[32] Kim S J, Park S J, Kim S I. Swelling behavior of interpenetrating polymer network hydrogels composed of poly(vinyl alcohol) and chitosan. React Funct Polym, 2003, 55: 53-59.
[33] Costa P, Lobo J M S. Modeling and comparison of dissolution profiles. Eur J Pharm Sci, 2001,13:123-133.
[34]Korsmeyer R W,Gurny R,Peppas N A,et al.Mechanism of solute release from porous hydrophilic polymers.Int J Pharm,1983,15:25-35.
[35]Peppas N A.Analysis of Fickian and non-Fickian drug release from polymers.Pharm Acta Helv,1985,60:110-111.
[36]Sagara K,Kim S W.A new synthesis of galactose-poly(ethylene glycol)-polyethylenimine for gene delivery to hepatocytes.J Control Release,2002,79:271-281.
[37]顾雪蓉,朱育平。凝胶化学。北京:化学工业出版社,2005,128-137.
[38]Hiemstra C,Zhong Z Y,Feijen J,et al.Release of model proteins and basic fibroblast growth factor from in situ forming degradable dextran hydrogels.J Control Release,2007,122:71-78.
[39]Yin L C,Ding J Y,Fei L K,et al.Beneficial properties for insulin absorption using superporous hydrogel containing interpenetrating polymer network as oral delivery vehicles.Int J Pharm,2008,350:220-229
[40]Kim B S,Mooney D J.Development of biocompatible synthetic extracellular matrices for tissue engineering.Trends in Biotech,1998,16:224-225.
[41]Langer R S,Vacanti J P.Tissue Engineering.Science,1993,260:920-926.
[42]Underhill G H,Chen A A,Bhatia S N,et al.Assessment of hepatocellular function within PEG hydrogels.Biomaterials,2007,28:256-270.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |