Langmuir 2002, 18, 2013-2018
2013
Thermosensitive Poly(N-isopropylacrylamide-co-acrylic acid) Hydrogels with Expanded Network Structures and Improved Oscillating Swelling-Deswelling Properties Xian-Zheng Zhang,† Yi-Yan Yang,*,† Fan-Jing Wang,† and Tai-Shung Chung†,‡ Institute of Materials Research and Engineering, 3 Research Link, Singapore 117602, Singapore, and Department of Chemical and Environmental Engineering, National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260, Singapore Received August 20, 2001. In Final Form: December 21, 2001 In this paper, a P(NIPAAm-co-AAc) hydrogel with rapid temperature sensitivity and improved oscillatory properties over small temperature cycles around the physiologic temperature of 37 °C was synthesized in an alkaline solution (Tris/HCl solution, pH 8.8 and I ) 0.5 M). SEM micrographs revealed that the unique properties achieved can be attributed to the expanded network structure generated in the alkaline solution during the copolymerization reaction. As a result of the dissociation of the carboxyl groups (-COOH) of AAc to carboxylate anions (-COO-), the electrostatic repulsion between carboxylate anions was strong and led to the expanded conformations of polymer chains. Therefore, the network of the hydrogels thus obtained was extremely expanded and exhibited fast temperature sensitivity and improved oscillating swelling-deswelling properties.
Introduction Recently, the use of polymeric three-dimensional materials as scaffolding materials has received considerable attention.1-8 These three-dimensional matrixes are usually made from poly(glycolic acid),2 poly(lactic acid),4 alginate,6,7 and agarose.8 Among these materials, the thermosensitive poly(N-isopropylacrylamide-co-acrylic acid) [P(NIPAAm-co-AAc)] hydrogel has been found to be a promising matrix, for example, as the extracellular matrix for the artificial pancreas.9-11 It is well-known that poly(N-isopropylacrylamide) (PNIPAAm) is a typical thermosensitive polymeric material that demonstrates a transition temperature (Ttr) or lower critical solution temperature (LCST) at ∼32 °C in aqueous solution.12 This type of temperature-sensitive polymer can be cross-linked to produce swellable hydrogels * To whom correspondence should be addressed. Tel.: 658748373. Fax: 65-8727528. E-mail:
[email protected]. † Institute of Materials Research and Engineering. ‡ National University of Singapore. (1) Freed, L. E.; Grande, D. A.; Lingbin, Z.; Emmanual, J.; Marquis, J. C.; Langer, R. J. Biomed. Mater. Res. 1994, 28, 891-899. (2) Seckel, B. R.; Jones, D.; Hekimian, K. J.; Wang, K.-K.; Chakalis, D. P.; Costas, P. D. J. Neurosci. Res. 1995, 40, 318-324. (3) Ellis, D. L.; Yannas, I. V. Biomaterials 1996, 17, 291-299. (4) Vernon, B.; Gutowska, A.; Kim, S. W.; Bae, Y. H. Macromol. Symp. 1996, 109, 155-167. (5) Whang, K.; Tsai, D. C.; Nam, E. K.; Aitken, M.; Sprague, S. M.; Patel, P. K.; Healy, K. E. J. Biomed. Mater. Res. 1998, 42, 491-499. (6) Maki, T.; Ubhi, C. S.; Sanchez-Farpon, H.; Sullivan, S. J.; Borland, K.; Muller, T. E.; Solomon, B. A.; Chick, W. L.; Monaco, A. P. Transplantation 1991, 51, 43-51. (7) Sullivan, S. J.; Maki, T.; Borland, K. M.; Mahoney, M. D.; Solomon, M. A.; Muller, T. E.; Monaco A. P.; Chick, W. L. Science 1991, 252, 718-721. (8) Iwata, H.; Amemiya, H.; Matsuda, T.; Takano H.; Hayashi, R. Diabetes 1989, 38, 224-225. (9) Vernon, B.; Gutowska, A.; Kim, S. W.; Bae, Y. H. Macromol. Symp. 1996, 109, 155-167. (10) Vernon, B.; Kim, S. W.; Bae, Y. H. J. Biomater. Sci., Polym. Ed. 1999, 10, 183-198 1999 (11) Vernon, B.; Kim, S. W.; Bae, Y. H. J. Biomed. Mater. Res. 2000, 51, 69-79. (12) Taylor, L. D.; Cerankowski, L. D. J. Polym. Sci. A: Polym. Chem. 1975, 13, 2551-2569.
through redox radical polymerization.13,14 The resulting three-dimensional PNIPAAm network undergoes phase separation as the external temperature cycles about the LCST.15 The thermoreversible property of phase separation has a variety of applications in many fields, including solute extraction and separation,16 controlled drug release,17 artificial organs,18 and enzyme immobilization.19 However, the PNIPAAm homopolymeric hydrogel is not a favored matrix for biomedical applications because of its transition temperature and rigid network structure. A desirable phase transition temperature of the threedimensional matrix should be at or near the physiologic temperature (37 °C). In addition, the gel matrix should possess high water content but still exhibit temperaturesensitive properties at 37 °C.11 Thus, incorporating a hydrophilic monomer, acrylic acid (AAc), into the PNIPAAm backbone is a good approach to modulating the properties of PNIPAAm hydrogel. However, as reported previously, an increased AAc content in the copolymer network can reduce or even eliminate its temperature sensitivity.20-23 In this paper, we aimed to develop P(NIPAAm-co-AAc) hydrogels with improved temperature sensitivity and oscillatory properties over small temperature cycles. The (13) Oh, J. S.; Kim, J. M.; Lee, K. J.; Bae, Y. C. Eur. Polym. J. 1999, 35, 621-630. (14) Wu, S.; Jorgensen, J. D.; Skaja, A. D.; Williams, J. P.; Soucek, M. D. Prog. Org. Coat. 1999, 36, 21-33. (15) Hirokawa, Y.; Tanaka, T. J. Chem. Phys. 1984, 81, 6379-6380. (16) Hoi, Y. J.; Yamaguchi, T.; Nakao, S. Ind. Eng. Chem. Res. 2000, 39, 2491-2495. (17) Ichikawa, H.; Fukumori, Y. J. Controlled Release 2000, 63, 107119. (18) Verrion, B.; Kim, S. W.; Bae, Y. H. J. Biomed. Mater. Res. 2000, 51, 69-79. (19) Liu, F.; Tao, G. L.; Zhuo, R. X. Polym. J. 1993, 25, 561-567. (20) Beltran, S.; Baker, J. P.; Hooper, H. H.; Blanch, H. W.; Prausnitz, J. M. Macromolecules 1991, 24, 549-551. (21) Gutowska, A.; Bae, Y. H.; Feijan, J.; Kim, S. W. J. Controlled Release 1992, 22, 95-104. (22) Yu, H.; Grainger, D. W. J. Appl. Polym. Sci. 1993, 49, 15531563. (23) Feil, H.; Bae, Y. H.; Feijan, J.; Kim, S. W. Macromolecules 1993, 26, 2496-2500.
10.1021/la011325b CCC: $22.00 © 2002 American Chemical Society Published on Web 02/21/2002
2014
Langmuir, Vol. 18, No. 6, 2002
Zhang et al.
Table 1. Feed Composition of the Temperature-Sensitive P(NIPAAm-co-AAc) Hydrogels (NA1-NA4) Synthesized in Alkaline Solution sample ID component
NA1
NA2
NA3
NA3
NIPAAm (mmol) AAc (mmol) BIS (mmol) Tris/HCl solution (mL)a 5 wt % APS (µL) TEMED (µL)
0.88 0.0145 0.013 2.0 20 5
0.88 0.029 0.013 2.0 20 5
0.88 0.0435 0.013 2.0 20 5
0.88 0.58 0.013 2.0 20 5
a
pH 8.8, I ) 0.5 M.
P(NIPAAm-co-AAc) hydrogels were synthesized in an alkaline solution (Tris/HCl solution, pH 8.8, I ) 0.5 M) and neutral water (I ) 0.5 M). The morphologies, swelling, deswelling, reswelling, and oscillating swelling-deswelling kinetics of the resultant hydrogels were investigated. Experimental Section Materials. N-isopropylacrylamide (NIPAAm, Aldrich Chemical Co., Inc., Milwaukee, WI) was purified by recrystallization three times from a mixed solvent of benzene and n-hexane. Acrylic acid (AAc, Aldrich Chemical Co., Inc.) was purified by vacuum distillation at 39 °C and 10 mmHg. N,N′-methylenebisacrylamide (BIS, Bio-Rad Laboratories, Hercules, CA), ammonium persulfate (APS, Bio-Rad Laboratories), and N,N,N′,N′-tetramethylethylenediamine (TEMED, Bio-Rad Laboratories) were used as received. Synthesis of the Hydrogels. Monomers NIPAAm and AAc were dissolved in the Tris/HCl solutions with different pH values (pH ) 8.8 and 7.0, respectively) and the same ionic strength (I ) 0.5 M) in the presence of the cross-linker BIS. APS was used as the initiator, and TEMED was added as an accelerator. Polymerization was carried out at room temperature (22 °C) for 15 h, and the resulting hydrogels were immersed in ultrapure water (18.2 MΩ cm) at 22 °C for at least 8 days. During this period, the ultrapure water was replaced with fresh ultrapure water at least four times daily to leach out the unreacted chemicals and allow the hydrogels to reach equilibrium in ultrapure water. The feed compositions of the monomers and other reactants are listed in Table 1. The P(NIPAAm-co-AAc) hydrogels prepared in the neutral (pH 7.0) and alkaline (pH 8.8) solutions are denoted NNA and NA, respectively. Surface Morphology. For the morphological studies, the hydrogel samples were first immersed in ultrapure water for at least 48 h to reach equilibrium. Then, the swollen hydrogel samples were freeze-dried for 24 h. The surface morphology of the freeze-dried gels was investigated by using a scanning electron microscope (SEM, XL Series-30, Philips, Hillsboro, OR). Specimens were coated with gold for 30 s in SEM coating equipment (JFC-1200 fine coater, JEOL, Tokyo, Japan). Measurement of the Swelling Ratio. The swelling ratios of hydrogel samples were measured in the temperature range from 22 to 60 °C using a gravimetric method. At each particular temperature, hydrogel samples were incubated in ultrapure water for at least 24 h and then removed, wiped with moistened filter paper to remove water from the sample surfaces, and weighed. The temperature was controlled by a thermostatic water bath (Grant precision stirred bath, Grant Instruments Ltd., Cambridge, U.K.) with a precision of (0.1 °C. Here, the swelling ratio is defined as the weight of water adsorbed in the swollen gel (Ws) divided by the dried weight of the gel (Wd). Measurement of the Deswelling Kinetics. The deswelling kinetics of the hydrogels was measured gravimetrically at 60 °C after the sample surfaces had been wiped with moistened filter paper to remove water. The hydrogel samples reached equilibrium in ultrapure water at 22 °C and were then transferred to hot ultrapure water at 60 °C. At regular time intervals, hydrogel samples were removed and weighed. Water retention is defined as 100 × (Wt - Wd)/Ws, where Wt is the weight of hydrogel and the other symbols are the same as defined above. Measurement of the Reswelling Kinetics. The swollen gel samples were first freeze-dried for at least 24 h, and the dried
gel samples were immersed in ultrapure water to reabsorb water at 22 °C. During the reswelling course, the samples were removed and weighed after being wiped with moistened filter paper to remove water from the sample surfaces. Water uptake is defined as 100 × (Wt - Wd)/Ws, and the symbols are the same as defined above.
Results and Discussion As a result of the incorporation of the ionizable groups of the comonomer AAc, P(NIPAAm-co-AAc) hydrogel can respond to changes in the temperature, pH, and ionic strength. The effects of pH, ionic strength, and AAc content on the properties of hydrogels have been intensively studied.24-28 The main purpose of this paper is to investigate the effect of the alkaline solution during the copolymerization process on the temperature-sensitive kinetics of the hydrogel. Ultrapure water was used during the characterization of the hydrogel to eliminate the influence of pH and ionic strength in the aqueous medium. Synthesis of the Hydrogel. Usually, P(NIPAam-coAAc) hydrogels are prepared by free-radical polymerization in organic solvents or water with the existence of monomers, cross-linkers, and redox initiators, as illustrated in Figure 1. In this work, we employed an alkaline solution as the polymerization solvent, and we expected to obtain P(NIPAAm-co-AAc) hydrogels with improved properties for potential applications in biomedical engineering. As the copolymerization was carried out in an alkaline solution, the dissociation of the -COOH moieties in the AAc molecules to -COO- caused the electrostatic repulsions among AAc carboxylate anions (-COO-) to be strong, which could have led to expanded conformations of the resultant polymer chains. Therefore, the expanded network of the hydrogel might have had an extremely high water uptake. Because the hydrogel structure is reported to retain memory of its formation history and molecular conformation,29-31 an expanded network structure with a special conformation would remain even after the hydrogel had been transferred to ultrapure water after the synthesis and after -COO- had changed to -COOH again. According to the mean-field theory, an expanded network with an increased osmotic pressure results in a rapidly discontinuous volume change during the phase transition.15,32,33 Thus, a hydrogel with an expanded network could have great temperature sensitivity. Because of the screening and salting-out effects of high electrolyte concentrations,34-36 the ionic strength in the alkaline solution was set at 0.5 M. On the other hand, the temperature sensitivity of P(NIPAAm-co-AAc) (24) Budtova, T.; Navard, P. Macromolecules 1996, 29, 3931-3936 (25) Bonapasta, A. A. Chem. Mater. 2001, 13, 64-70. (26) Robb, I. D.; Stevenson, P. Langmuir 2000, 16, 7168-7172. (27) Petrovic, S. C.; Zhang, W.; Ciszkowska, M. Anal. Chem. 2000, 72, 3449-3454. (28) Shibanuma, T.; Aoki, T.; Sanui, K.; Ogata, N.; Kikuchi, A.; Sakurai, Y.; Okano, T. Macromolecules 2000, 33, 444-450. (29) Panyukov, S.; Rabin, Y. Phys. Rep. 1996, 269, 1-131. (30) Nakamoto, C.; Motonaga, T.; Shibayama, M. Macromolecules 2001, 34, 911-917. (31) Alvarez-Lorenzo, C.; Guney, O.; Oya, T.; Sakai, Y.; Kobayashi, M.; Enoki, T.; Takeoka, Y.; Ishibashi, T.; Kuroda, K.; Tanaka, K.; Wang, G.; Yu, A.; Masamune, G. S.; Tanaka, T. Macromolecules 2000, 33, 8693-8697. (32) Dusek, K.; Patterson, D. J. Polym. Sci. A: Polym. Chem. 1968, 6, 1209-1214. (33) Tanaka, T.; Fillmore, D. J.; Sun, S. T.; Nishio, I.; Swislow, G.; Shah, A. Phys. Rev. Lett. 1980, 45, 1636-1639. (34) Yu, H.; Grainger, D. W. J. Appl. Polym. Sci. 1993, 49, 15531563. (35) Beltran, S.; Baker, J. P.; Hooper, H. H.; Blanch, H. W.; Prausnitz, J. M. Macromolecules 1991, 24, 549-551. (36) Ebara, M.; Aoyagi, T.; Sakai, K.; Okano, T. Macromolecules 2000, 33, 8312-8316.
Thermosensitive P(NIPAAM-co-AAc) Hydrogels
Langmuir, Vol. 18, No. 6, 2002 2015
Figure 1. Synthesis scheme of P(NIPAAm-co-AAc) hydrogels by radical copolymerization using BIS as the cross-linker.
Figure 2. Schematic illustration of the structures of conventional PNIPAAm and P(NIPAAm-co-AAc) hydrogels as well as an expanded P(NIPAAm-co-AAc) hydrogel.
hydrogel decreases with increasing pH value.36 Therefore, an alkaline solution with pH values that are too high is not favorable. On the basis of these considerations, a Tris/ HCl solution with a pH of 8.8 and an ionic strength of 0.5 M was chosen as the copolymerization solvent for the synthesis of P(NIPAAm-co-AAc) hydrogel. Schematic structures of PNIPAAm and conventional P(NIPAAmco-AAc) and expanded P(NIPAAm-co-AAc) hydrogels are provided in Figure 2. Morphology of the Hydrogels. SEM images of freezedried gel samples are shown in Figure 3. In a comparison with NNA hydrogels, it can be seen that the gel network expanded from NNA1 to NNA4 with an increase in the AAc content, in agreement with the conventional explanation for the incorporation of AAc into PNIPAAm network.24,25,28 Compared to the NNA gels, the networks of the NA gels were much more expanded. This directly
supports our above hypothesis that a highly expanded network can be generated by the repulsions among AAc carboxylate anions (-COO-) in the alkaline copolymerization solvent. The hydrogen bonds between the carboxyl groups (-COOH) of the AAc units and the amide groups (-CONH) kept the polymer chains of the NNA1-NNA4 and NA1NA4 hydrogels close to each other and restricted the expansion of the network at temperatures below their LCSTs. On the other hand, the uptake of more water as a result of the incorporation of hydrophilic AAc comonomer resulted in the expansion of the gel matrixes and counterbalanced the effect of hydrogen bonds. With increasing AAc content, the expansion of the gel matrixes became dominant, although the number of hydrogen bonds also might have become greater. Thus, the gel network had a more expanded structure with an increased AAc content. Swelling Ratio at Room Temperature. It is known that a hydrophilic/hydrophobic balance exists in the PNIPAAM network because of its hydrophilic and hydrophobic nature.12,16 Hydrogen bonds between water molecules and hydrophilic groups lead to the good solubility of the PNIPAAm hydrogel at low temperatures. When the external temperature is increased to the LCST, the hydrophobic interactions among the hydrophobic groups overwhelm the hydrogen bonds, and phase separation occurs.37-40 Here, as the hydrophilic monomer AAc was introduced into the backbone of the gel, the hydrophilic/ (37) Matsuo, E. S.; Tanaka, T. J. Chem. Phys. 1988, 89, 1695-1703. (38) Inomato, H.; Goto, S.; Saito, S. Macromolecules 1990, 23, 48874888.
2016
Langmuir, Vol. 18, No. 6, 2002
Zhang et al.
Figure 3. SEM micrographs of the conventional (left) and expanded P(NIPAAm-co-AAc) (right) hydrogels. The size of the bar is 20 µm.
hydrophobic ratio of the gel network was increased, and the hydrophilicity of the gel as a whole improved, leading to an increasing water content at room temperature. Figure 4 shows the dependence of the equilibrium swelling ratio at room temperature on the AAc content of the P(NIPAAm-co-AAc) hydrogels. One can observe that, at room temperature, the swelling ratio of conventional AAc-incorporated PNIPAAm gels (NNA) prepared in a neutral solution increased linearly with increasing AAc (39) Tokuhiro, T.; Amiya, T.; Mamada, A.; Tanaka, T. Macromolecules 1991, 24, 2936-2943. (40) Otake, K.; Inomata, H.; Konno, M.; Saito, S. Macromolecules 1990, 23, 3, 283-289.
content. The swelling ratios of the expanded AAcincorporated PNIPAAm gels (NA), synthesized in the alkaline solution, were higher than those of the NNA gels, and the difference turned out to be more significant for higher AAc contents. This difference is attributed to the expanded network structure generated by the repulsion of the AAc carboxylate anions (-COO-) formed in the alkaline solution during the polymerization process. With increasing AAc content, the number of carboxylate anions increased, and the electrostatic repulsion between polymer chains was strengthened. Thus, an extremely expanded conformation of the gel matrixes was produced at high AAc contents.
Thermosensitive P(NIPAAM-co-AAc) Hydrogels
Langmuir, Vol. 18, No. 6, 2002 2017
Figure 4. Swelling ratios of the conventional and expanded P(NIPAAm-co-AAc) hydrogels at room temperature (22 °C).
Figure 6. Deswelling kinetics of the conventional and expanded P(NIPAAm-co-AAc) hydrogels at 60 °C.
Figure 5. Temperature dependence of the swelling ratio of the conventional and expanded P(NIPAAm-co-AAc) hydrogels in the temperature range from 22 to 60 °C.
Temperature Dependence of the Swelling Ratio. Figure 5 shows the equilibrium swelling ratio of poly(NIPAAm-co-AAc) hydrogels in ultrapure water as a function of external temperature. At temperatures below the LCST, the swelling ratios of the NA gels were larger than those of the corresponding NNA gels, as already explained. In the case of NA1 and NNA1, the swelling ratios of the two gels slightly increased from room temperature (22 °C) to 28 °C. This is probably due to the destruction of hydrogen bonds between the hydrophilic carboxyl groups. As the temperature was increased in the range below the phase transition temperature, the driving force for network expansion resulting from the destruction of the hydrogen bonds overwhelmed the driving force for breakdown of the hydrophobic interactions between the hydrophobic groups. Thus, the networks of NA1 and NNA1 were slightly expanded. This phenomenon was not observed for gels with higher AAc contents because the high hydrophilic nature of AAc minimizes the destruction of the hydrogen bonds below the LCST. These gels exhibited a decreased swelling ratio when the temperature was increased because the hydrophobic interactions between the hydrophobic groups of the gels became dominant and, thus, the gel matrixes shrank. Usually, the transition temperature or LCST of a hydrogel is defined as the temperature at which the swelling ratio decreases to one-half of its value at the
initial temperature or room temperature.41 From Figure 5, it can be seen that the LCSTs of the hydrogels increased with increasing AAc content. Comparing the LCSTs of NA and NNA hydrogels with the same AAc content, no obvious shift was found because the LCST is determined mainly by the chemical composition of the hydrogels. Accurate LCSTs for the AAc-incorporated PNIPAAm hydrogels were reported in previous publications.11,42,43 Although the LCSTs of the NA and NNA hydrogels remained unchanged at the same AAc content, the dimensional changes of the NA hydrogels during phase separation were much greater than those of the NNA hydrogels. This implies that the temperature sensitivity of the NA hydrogels with expanded network structures was improved. Deswelling Kinetics. Figure 6 shows the shrinking kinetics of poly(NIPAAm-co-AAc) hydrogels after a temperature jump from the equilibrated swollen state at 22 °C (below the LCST) to ultrapure water at 60 °C above the LCST. It can be clearly seen that the shrinking rates of the NA hydrogels were much higher than those of the NNA hydrogels. For example, after being immersed in ultrapure water with a temperature of 60 °C for 17 min, hydrogels NA1-NA4 shrank and lost water to the extent of over 65, 55, 56, and 53%, respectively. In contrast, about 50, 36, 35, and 27% of the water was freed from NNA1NNA4, respectively. The improvement in the deswelling kinetics of the NA hydrogels might occur for the following reasons: According to mean-field theory, if the network expanded, the chemical potential difference between inside and outside the hydrogels would increase, which would lead to an increase in the osmotic pressure within the gel matrix. As a consequence, sudden dimensional changes would occur, and the hydrogel would exhibit a discontinuous phase transition.32,33 In the expanded state, the mobility of the polymer chains was much higher; thus, the gel synthesized in the alkaline solvent would deswell faster. On the other hand, because of the increased thermal energy at 60 °C (41) Wu, X. S.; Hoffman, A. S.; Yager, P. J. Polym. Sci. A: Polym. Chem. 1992, 30, 2121-2129. (42) Shibayama, M.; Fujikawa, Y.; Nomura, S. Macromolecules 1996, 29, 9, 6535-6540. (43) Shibayama, M.; Kawakubo, K.; Norisuye, T. Macromolecules 1998, 31, 1608-1614.
2018
Langmuir, Vol. 18, No. 6, 2002
Zhang et al.
Figure 8. Oscillating swelling-deswelling kinetics of the conventional and expanded P(NIPAAm-co-AAc) hydrogels over 5-min temperature cycles between 35 and 40 °C. Figure 7. Reswelling kinetics of the freeze-dried conventional and expanded P(NIPAAm-co-AAc) hydrogels at 22 °C.
above the LCST, the polymer chains would become more mobile, and the increased hydrophobic interactions among polymer chains would drive water out and cause the chains to collapse and entangle. Thus, a solidlike aggregated state would be formed.39 During deswelling, the entropy of the polymer chains would decrease, whereas the entropy of the water surrounding the polymer chains would increase. However, the total entropy of the gel system (polymer chains and the solvent) would increase because the phase transition of temperature-sensitive gels is an entropydriven process.40,44-46 In the case of the expanded NA hydrogels, because of the expanded polymer chains, the number of surrounding structured water molecules was greater, and the entropy of the gel system was decreased. The expanded gel system tended to collapse and undergo phase separation, compared with the conventional gel system, as the temperature was increased. When the temperature was increased above the LCST, the expanded polymer chains quickly dehydrated and exhibited rapid deswelling, resulting in an abrupt phase transition. In addition, fast water diffusion within the expanded gel matrix might also be a reason for the rapid deswelling kinetics. Reswelling Kinetics. Figure 7 illustrates the reswelling ratio of freeze-dried poly(NIPAAm-co-AAc) gels in ultrapure water at room temperature (22 °C). All of the dried gels exhibited relatively lower rates of reswelling than deswelling because of the strong hydrophobic interactions between the tightly entangled polymer chains in the dried state. The shrunken gel matrix was difficult to hydrate.41 Comparing the reswelling ratios of the NA and NNA gels, one can see that the NA gels reswelled much more rapidly than the NNA gels. This was because the expanded NA matrixes (Figure 3) provided less tortuosity for water diffusion, resulting in quicker hydration of the polymer chains. Oscillating Swelling-Deswelling Properties. The above investigations show that hydrogels with expanded network structures exhibit faster deswelling and reswelling kinetics. From an application standpoint, it is necessary to study the kinetics of oscillating swelling(44) Kayaman, N.; Kazan, D.; Erarslan, A.; Okay, O.; Baysal, B. M. J. Appl. Polym. Sci. 1998, 67, 805-814. (45) Okazaki, S.; Nakanishi, K.; Touhara, H. J. Chem. Phys. 1983, 78, 454-469. (46) Luan, C. H.; Urry, D. W. J. Phys. Chem. 1991, 95, 7896-7900.
deswelling in response to small temperature cycles around the physiologic temperature. The oscillating swellingdeswelling properties of poly(NIPAAm-co-AAc) gels were investigated, and the results are shown in Figure 8. Gels NA1, NA2, NNA1, and NNA2 swelled and deswelled in ultrapure water over 5-min temperature cycles between 35 and 40 °C. It can be observed that, during the swellingdeswelling process, the swelling ratios of the gels decreased with increasing number of cycles. This is because reswelling is slower than deswelling. From Figure 8, it can also be observed that, with an increase in the content of nonthermosensitive AAc, the magnitude of the oscillating swelling-deswelling was reduced. However, a more rapid and larger-magnitude swelling-deswelling was achieved with NA gels owing to their expanded structures. Thus, the P(NIPAAm-co-AAc) hydrogels, synthesized in alkaline solution, would be more favorable for biomedical applications, compared to the conventional P(NIPAAm-co-AAc) hydrogels. Conclusion P(NIPAAm-co-AAc) hydrogels were synthesized in alkaline solution (Tris/HCl, pH 8.8, I ) 0.5 M). As a result of the electrostatic repulsion between the carboxylate anions (-COO-) of the polymer chains formed in the alkaline solution, an extremely expanded gel structure was obtained, and the gel matrix became more porous with increasing AAc content. The expanded P(NIPAAmco-AAc) gel matrixes exhibited larger swelling ratios and absorbed more water at room temperature than the conventional P(NIPAAm-co-AAc) gels. On the other hand, these gels showed higher deswelling rates at 60 °C, and the freeze-dried gels also underwent faster reswelling at room temperature. The oscillating swelling-deswelling kinetics of P(NIPAAm-co-AAc) gels was investigated. The P(NIPAAm-co-AAc) gels with expanded structures prepared in alkaline solution exhibited a greater magnitude of change in volume during the oscillating swellingdeswelling process, indicating their potential for applications in the biomedical field. Acknowledgment. This research was supported by a grant from the National Science and Technology Board of Singapore. LA011325B
