快速响应性PNIPA智能水凝胶的合成、表征及应用研究
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摘要
聚N-异丙基丙烯酰胺(PNIPA)智能水凝胶作为一种温度敏感性材料，近年来在应用中取得了初步进展，并越来越受到人们的重视。目前，一部分工作集中在凝胶响应机制的理论解释及实验验证；另一部分工作通过NIPA与其它单体的共聚，以期实现对材料的改性，从而获得多重敏感性的凝胶，以实现在各个领域中的应用。
PNIPA智能水凝胶的智能性主要体现在两个方面：(1)PNIPA在相转变温度(LCST)附近，随温度的微小变化，凝胶的溶胀度具有很大的突变性；(2)PNIPA在LCST附近的溶胀度变化速率很快(快速响应性)。目前制备的PNIPA水凝胶大都具有响应速度慢的缺点，往往不能从以上两方面同时体现出其智能性；而PNIPA水凝胶的响应速率是一个极为重要的参数，在很多情况下都要求其对外界温度刺激具有较快的响应速率，这就大大限制了温敏性PNIPA智能水凝胶的使用范围。因此，提高快速响应性一直是智能水凝胶研究的一个重要课题。
目前，对提高PNIPA智能水凝胶快速响应性的基础研究相对较少。这是由于影响因素较多，而研究手段却较少。文献中已报道的提高其响应速率的方法有以下几种：(1)合成小尺寸的PNIPA微凝胶。由于研究手段的限制，此类研究在理论方面发展较慢，在实际应用中也没有获得突破性进展，应用范围极为有限。(2)合成含孔的PNIPA水凝胶。在PNIPA智能凝胶结构中引入孔洞的方法提高了凝胶的响应速率，但是凝胶的强度相对降低了很多；同时由于其结构上的特点，降低了其适用的范围。例如，在凝胶的浓缩分离过程中，由于孔洞结构吸附了大量的生物大分子，从而降低了浓缩效率。(3)利用相分离技术合成PNIPA水凝胶。此法得到的PNIPA水凝胶具有较快的响应速率，但对反应时间和温度的控制非常关键。由于对凝胶化时间难以作出精确的判断，合成的PNIPA水凝胶重现性较差，且呈乳白色；与常规方法合成的PNIPA水凝胶相比，其机械强度也下降很多；此法合成的PNIPA水凝胶难以在实际中使用。(4)接枝共聚合成PNIPA水凝胶。将NIPA单体接枝到其它基体上，合成具有特定结构的PNIPA水凝胶。一方面，上述特定结构单体的合成过程复杂，很难在实际中得到应用；另一方面，所合成的共聚物由于PNIPA含量的限制，水凝胶在LCST前后的溶胀性能有所减弱，智能性有所降低。
本工作以N-异丙基丙烯酰胺为单体，N，N’—亚甲基双丙烯酰胺为交联剂制备了一系列智能性水凝胶。从理论和应用的角度出发，以提高PNIPA水凝胶的智能性为目的，首先以宏观PNIPA智能水凝胶为对象，重点研究凝胶的尺寸对凝胶响应速率的影响，并将由此得到的理论应用到微观凝胶的研究中去，克服了微观凝胶研究手段的限制；然后将得到的凝胶进行应用试验。同时，还对PNIPA智能水凝胶的响应机理进行探讨。
(1)采用传统的化学引发法，用溶液聚合制备了一系列不同直径(湿凝胶，3.12～2.8mm)、不同厚度(湿凝胶，3～12mm)的PNIPA宏观智能水凝胶；将一部分凝胶粉碎制得不同尺寸的(干凝胶，0.154～0.9mm)粒状凝胶。
首先研究了聚合条件对PNIPA智能水凝胶性能的影响，在最佳制备条件(T≤10℃，7％≤C_(NIPA)≤12％，2％≤C_(MBA)≤4％)时可以得到透明、溶胀度较高、性能均一的PNIPA智能水凝胶。
然后研究了水凝胶的溶胀一消溶胀、脱水一吸水过程与凝胶尺寸的关系。结果表明，在
凝胶处于消溶胀和干燥状态下时，凝胶块容易形成一种壳—核结构。在核中是被包裹的水
分子，由于外面的壳层比较致密，其内部的水很难扩散出。且随着凝胶直径和厚度的增大，
其内部包括的水的含量也急剧增加;而对于尺寸更小的粉状凝胶，其形成的壳层和核层的比
例相差不大，其溶胀性能受尺寸的影响很小。
凝胶达平衡溶胀所需的时间与凝胶尺寸之间的关系可以用式:刀功。=K(肠。)。x(MT)，
作为普适方程来应用。对于尺寸较小的凝胶，由于表征手段的限制，可以由此方程进行外推，
取得了较好的效果。由此可作为制备和使用快速响应性智能水凝胶的理论依据。
(2)分别采用无皂乳液聚合和反相乳液聚合的方法制备了一系列不同尺寸的微凝胶，
分析制备条件对微凝胶的影响。结果表明，采用反相悬浮聚合可以制得粒径较大的智能水凝
胶(D:ll pm)，采用无皂乳液聚合在不同条件下合成一系列不同尺寸的微凝胶(D扣.12“m~
4.5协m);分别采用激光光散射和偏光显微镜对微凝胶的大小、形态进行表征，也得到了一
致结果;采用紫外一可见分光光度计可以定性地研究微凝胶的相转变现象。
将由宏观凝胶得到的理论公式应用到微观凝胶的溶胀动力学中，可以初步估计微凝胶达
平衡溶胀所需的时间，定量的体现快速响应性智能水凝胶的智能性。
(3)将不同尺寸的宏观凝胶和微观凝胶分别对牛血红蛋白进行固定化，研究凝胶尺寸
对牛血红蛋白活性的影响，分析PNI以智能凝胶对牛血红蛋白活性的控制机理。结果表明，
在PH=6 .0，C。=3 .5%时，PNIPA凝胶对酶的活性具有很好的可控性;尺寸较小的粉状凝胶和
由悬浮聚合得到的微凝胶，由于其对温度的快速响应性，其对牛血红蛋白的活性的控制效果
很好，充分体现了快速响应性智能水凝胶的智能性。
(4)以褪黑素为模型药物，研究释放条件?
As a kind of temperature-sensitive material, the application of Poly(N-isopropylacrylamide) (PNIPA) intelligent hydrogels has been achieved primary development and got much intention in recent years. At the present time, studies are focused both on theoretic explanation and experimental verification for the stimuli-response mechanism, and on the copolymerization of NIPA with other monomers to modify their properties and obtain multi-sensitive hydrogels which are applied in wide fields.
Usually, the intelligent properties of hydrogels are shown into two aspects: (1) The hydrogels have discontinuous swelling ratios with little change of temperature near the LCST. (2) The hydrogels have rapid stimuli-response velocities. PNIPA hydrogels prepared by traditional methods have very slow stimuli-response velocities, which limits their application range.
Furthermore, the stimuli-response of PNIPA hydrogels is a very important parameter in application. The rapid stimuli-response velocity is needed in many cases. Therefore, the preparation and application are important task in research of intelligent hydrogels with rapid response velocity.
The reason of the limited research on theory and application for rapid response velocity is ascribed to the complicated influencing factors and little of characterization methods. There are several methods reported to increase the response speed in literature.
(1) Preparation of microgels by emulsion polymerization or other methods. But there are less techniques and methods for their characterization and development in theory, accordingly, there is little breakthrough in the practical application. Therefore, the use of this method is very limited.
(2) Synthesis of porous PNIPA hydrogels. Though the response speeds are enhanced, the reduced hydrogel intensity limits their application in much fields. For example, some bio-macromolecules can be absorbed into the hydrogel pores in separation, which reduces the separation efficiency.
(3) Manufacture by Phase Separation Technique. The PNIPA hydrogels have rapid response velocities, but the control of reaction time and temperature in preparation is much critical. Sometimes, the same hydrogels could hardly be achieved with different reaction time, and the hydrogels are often opaque and fragile. Thus, the hydrogels prepared by this method cannot be used practically too.
(4) Graft copolymerization. NIPA monomer is grafted onto the defined matrix to synthesize the functional material. Obviously, such hydrogels have rapid response velocities compared with the large bulk hydrogels, but there are also two shortcomings in this method. One is the complicated preparation of defined structure; the other is the seriously reduced swelling ratio near LCST due to the limited content of PNIPA.
In this paper, more attention was paid to two respects-swelling ratio and stimuli-response velocity to improve intelligent properties of PNIPA hydrogels.
(1) By traditional chemical initialing method, a series of macrogels with different diameter (3. 12~12. 8mm, wet state) and thickness (3~12mm, wet state) were obtained in solution polymerization. Some of these macrogels were smashed into particles with different diameter(0. 154~0. 9mm, dry state).
Firstly, the effects of polymerization conditions on the macrogels properties were conducted. The experiment results showed that the transparent, high swelling ratio and uniform macrogels could be manufactured at the optimized conditions (T^IO'C, Secondly, the relationship between the macrogels dimension and the swelling-deswelling, dehydration-soakage process was studied by different method. The results showed that the macrogels could form a shell-core structure easily under the deswelling or dry state. In this structure, some water was packed into the macrogels which could not diffuse out of the shell due to the outer compact shell. With the increase of diameter and thickness, the water content packed in the macrogels increased sharply. However, the swelling ratio was hardly affected by dimension for the smaller macrog
PNIPA智能水凝胶的智能性主要体现在两个方面：(1)PNIPA在相转变温度(LCST)附近，随温度的微小变化，凝胶的溶胀度具有很大的突变性；(2)PNIPA在LCST附近的溶胀度变化速率很快(快速响应性)。目前制备的PNIPA水凝胶大都具有响应速度慢的缺点，往往不能从以上两方面同时体现出其智能性；而PNIPA水凝胶的响应速率是一个极为重要的参数，在很多情况下都要求其对外界温度刺激具有较快的响应速率，这就大大限制了温敏性PNIPA智能水凝胶的使用范围。因此，提高快速响应性一直是智能水凝胶研究的一个重要课题。
目前，对提高PNIPA智能水凝胶快速响应性的基础研究相对较少。这是由于影响因素较多，而研究手段却较少。文献中已报道的提高其响应速率的方法有以下几种：(1)合成小尺寸的PNIPA微凝胶。由于研究手段的限制，此类研究在理论方面发展较慢，在实际应用中也没有获得突破性进展，应用范围极为有限。(2)合成含孔的PNIPA水凝胶。在PNIPA智能凝胶结构中引入孔洞的方法提高了凝胶的响应速率，但是凝胶的强度相对降低了很多；同时由于其结构上的特点，降低了其适用的范围。例如，在凝胶的浓缩分离过程中，由于孔洞结构吸附了大量的生物大分子，从而降低了浓缩效率。(3)利用相分离技术合成PNIPA水凝胶。此法得到的PNIPA水凝胶具有较快的响应速率，但对反应时间和温度的控制非常关键。由于对凝胶化时间难以作出精确的判断，合成的PNIPA水凝胶重现性较差，且呈乳白色；与常规方法合成的PNIPA水凝胶相比，其机械强度也下降很多；此法合成的PNIPA水凝胶难以在实际中使用。(4)接枝共聚合成PNIPA水凝胶。将NIPA单体接枝到其它基体上，合成具有特定结构的PNIPA水凝胶。一方面，上述特定结构单体的合成过程复杂，很难在实际中得到应用；另一方面，所合成的共聚物由于PNIPA含量的限制，水凝胶在LCST前后的溶胀性能有所减弱，智能性有所降低。
本工作以N-异丙基丙烯酰胺为单体，N，N’—亚甲基双丙烯酰胺为交联剂制备了一系列智能性水凝胶。从理论和应用的角度出发，以提高PNIPA水凝胶的智能性为目的，首先以宏观PNIPA智能水凝胶为对象，重点研究凝胶的尺寸对凝胶响应速率的影响，并将由此得到的理论应用到微观凝胶的研究中去，克服了微观凝胶研究手段的限制；然后将得到的凝胶进行应用试验。同时，还对PNIPA智能水凝胶的响应机理进行探讨。
(1)采用传统的化学引发法，用溶液聚合制备了一系列不同直径(湿凝胶，3.12～2.8mm)、不同厚度(湿凝胶，3～12mm)的PNIPA宏观智能水凝胶；将一部分凝胶粉碎制得不同尺寸的(干凝胶，0.154～0.9mm)粒状凝胶。
首先研究了聚合条件对PNIPA智能水凝胶性能的影响，在最佳制备条件(T≤10℃，7％≤C_(NIPA)≤12％，2％≤C_(MBA)≤4％)时可以得到透明、溶胀度较高、性能均一的PNIPA智能水凝胶。
然后研究了水凝胶的溶胀一消溶胀、脱水一吸水过程与凝胶尺寸的关系。结果表明，在
凝胶处于消溶胀和干燥状态下时，凝胶块容易形成一种壳—核结构。在核中是被包裹的水
分子，由于外面的壳层比较致密，其内部的水很难扩散出。且随着凝胶直径和厚度的增大，
其内部包括的水的含量也急剧增加;而对于尺寸更小的粉状凝胶，其形成的壳层和核层的比
例相差不大，其溶胀性能受尺寸的影响很小。
凝胶达平衡溶胀所需的时间与凝胶尺寸之间的关系可以用式:刀功。=K(肠。)。x(MT)，
作为普适方程来应用。对于尺寸较小的凝胶，由于表征手段的限制，可以由此方程进行外推，
取得了较好的效果。由此可作为制备和使用快速响应性智能水凝胶的理论依据。
(2)分别采用无皂乳液聚合和反相乳液聚合的方法制备了一系列不同尺寸的微凝胶，
分析制备条件对微凝胶的影响。结果表明，采用反相悬浮聚合可以制得粒径较大的智能水凝
胶(D:ll pm)，采用无皂乳液聚合在不同条件下合成一系列不同尺寸的微凝胶(D扣.12“m~
4.5协m);分别采用激光光散射和偏光显微镜对微凝胶的大小、形态进行表征，也得到了一
致结果;采用紫外一可见分光光度计可以定性地研究微凝胶的相转变现象。
将由宏观凝胶得到的理论公式应用到微观凝胶的溶胀动力学中，可以初步估计微凝胶达
平衡溶胀所需的时间，定量的体现快速响应性智能水凝胶的智能性。
(3)将不同尺寸的宏观凝胶和微观凝胶分别对牛血红蛋白进行固定化，研究凝胶尺寸
对牛血红蛋白活性的影响，分析PNI以智能凝胶对牛血红蛋白活性的控制机理。结果表明，
在PH=6 .0，C。=3 .5%时，PNIPA凝胶对酶的活性具有很好的可控性;尺寸较小的粉状凝胶和
由悬浮聚合得到的微凝胶，由于其对温度的快速响应性，其对牛血红蛋白的活性的控制效果
很好，充分体现了快速响应性智能水凝胶的智能性。
(4)以褪黑素为模型药物，研究释放条件?
As a kind of temperature-sensitive material, the application of Poly(N-isopropylacrylamide) (PNIPA) intelligent hydrogels has been achieved primary development and got much intention in recent years. At the present time, studies are focused both on theoretic explanation and experimental verification for the stimuli-response mechanism, and on the copolymerization of NIPA with other monomers to modify their properties and obtain multi-sensitive hydrogels which are applied in wide fields.
Usually, the intelligent properties of hydrogels are shown into two aspects: (1) The hydrogels have discontinuous swelling ratios with little change of temperature near the LCST. (2) The hydrogels have rapid stimuli-response velocities. PNIPA hydrogels prepared by traditional methods have very slow stimuli-response velocities, which limits their application range.
Furthermore, the stimuli-response of PNIPA hydrogels is a very important parameter in application. The rapid stimuli-response velocity is needed in many cases. Therefore, the preparation and application are important task in research of intelligent hydrogels with rapid response velocity.
The reason of the limited research on theory and application for rapid response velocity is ascribed to the complicated influencing factors and little of characterization methods. There are several methods reported to increase the response speed in literature.
(1) Preparation of microgels by emulsion polymerization or other methods. But there are less techniques and methods for their characterization and development in theory, accordingly, there is little breakthrough in the practical application. Therefore, the use of this method is very limited.
(2) Synthesis of porous PNIPA hydrogels. Though the response speeds are enhanced, the reduced hydrogel intensity limits their application in much fields. For example, some bio-macromolecules can be absorbed into the hydrogel pores in separation, which reduces the separation efficiency.
(3) Manufacture by Phase Separation Technique. The PNIPA hydrogels have rapid response velocities, but the control of reaction time and temperature in preparation is much critical. Sometimes, the same hydrogels could hardly be achieved with different reaction time, and the hydrogels are often opaque and fragile. Thus, the hydrogels prepared by this method cannot be used practically too.
(4) Graft copolymerization. NIPA monomer is grafted onto the defined matrix to synthesize the functional material. Obviously, such hydrogels have rapid response velocities compared with the large bulk hydrogels, but there are also two shortcomings in this method. One is the complicated preparation of defined structure; the other is the seriously reduced swelling ratio near LCST due to the limited content of PNIPA.
In this paper, more attention was paid to two respects-swelling ratio and stimuli-response velocity to improve intelligent properties of PNIPA hydrogels.
(1) By traditional chemical initialing method, a series of macrogels with different diameter (3. 12~12. 8mm, wet state) and thickness (3~12mm, wet state) were obtained in solution polymerization. Some of these macrogels were smashed into particles with different diameter(0. 154~0. 9mm, dry state).
Firstly, the effects of polymerization conditions on the macrogels properties were conducted. The experiment results showed that the transparent, high swelling ratio and uniform macrogels could be manufactured at the optimized conditions (T^IO'C, Secondly, the relationship between the macrogels dimension and the swelling-deswelling, dehydration-soakage process was studied by different method. The results showed that the macrogels could form a shell-core structure easily under the deswelling or dry state. In this structure, some water was packed into the macrogels which could not diffuse out of the shell due to the outer compact shell. With the increase of diameter and thickness, the water content packed in the macrogels increased sharply. However, the swelling ratio was hardly affected by dimension for the smaller macrog
引文
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