1487_book.fm Page 245 Friday, January 16, 2004 4:24 PM

13

Fast Swelling Hydrogel Systems

Richard A. Gemeinhart and Chunqiang Guo

CONTENTS

Introduction............................................................................................................245Polymer Swelling ..................................................................................................247Ideas for Rapid Swelling.......................................................................................248Superporous Hydrogels .........................................................................................249

Factors Affecting Synthesis of Superporous Hydrogel.............................249Swelling Kinetics of SPHs ........................................................................250Environmentally Sensitive SPHs...............................................................252

Summary ................................................................................................................254Future Considerations............................................................................................254References..............................................................................................................255

INTRODUCTION

There are many applications in which a material is needed to swell rapidly in a fluid.Materials that imbibe large volumes of water are very functional in daily use andin specialized applications. Everyday materials such as diapers and sanitary napkinsmust rapidly contain large volumes of biologic fluids and retain strength withoutlosing fluid to the surrounding areas.1 These materials are typically made of hydro-philic polymers that can swell in biologic fluids and will not dissolve.

Hydrogels were first described in the last century as networks that contain smallfractions of polymers and large fractions of water; hydrogels maintain their shapeswhile they imbibe fluids or are dried.2 Figure 13.1 is a representation of the structureof a hydrogel. When a hydrogel is in a dehydrated or deswollen state, its polymerchains are in close proximity with little room for diffusion of molecules. As thematerial swells, the polymer chains separate to an extent determined by the propertiesof the solvent in which the hydrogel has been placed. Under certain conditions, thepolymer chains will extend to the greatest extent possible and little interaction willtake place between the chains. In this state, the swelling pressure on the polymersis counteracted by the crosslinkers in the hydrogel; the mesh size (Figure 13.1) isgreatest, and diffusion of small molecules approaches the diffusion coefficient inpure fluid.

2450-8493-1487-9/04/$0.00+$1.50© 2004 by CRC Press LLC

246

Reflexive Polymers and Hydrogels

1487_book.fm Page 246 Friday, January 16, 2004 4:24 PM

Medical uses of hydrogels and other materials that swell rapidly in fluids havebeen the major areas of research in the last several decades. Absorbent sponges madeof materials that are similar to diapers have been produced with great success. Embolicagents are currently placed in the blood vessels of patients who would otherwisebleed to death.3 Embolic agents must swell quickly when placed in blood or theymay disperse from the site of administration and become problematic downstream.4

The materials cited in these examples may be used in a dehydrated state andswell upon placement in fluid. Other materials can swell rapidly when placed in anappropriate environment that contains a certain pH,5,6 temperature,7 electric field,8−10

light,11−14 pressure,15,16 or specific molecule.17−21 With the advent of nanotechnology,rapidly swelling and shrinking (deswelling) materials have been suggested as actu-ators in nanodevices.22−24 These materials require extreme sensitivity and speed forsensing their environments. The need for materials that swell quickly when placedin fluid is quite obvious. Depending upon the type of sensing necessary, problemswith speed of sensing, swelling or deswelling, and methods for increasing the speedof transition from deswollen to swollen or the reverse are being vigorously investi-gated.25 Diversity of applications for rapidly swelling materials is especially impor-tant because materials that are inexpensive to produce in any size and shape wouldproduce benefits for many areas of society, in particular medicine and drug delivery,26

although applications in other areas are suggested as well.24

In this chapter, we discuss methods that have been used to create rapidly swellinghydrogels and crosslinked polymeric systems. Chapter 12 by Ebara et al. discussesmaterials used in applications in which rapid shrinking (deswelling) is needed. Thischapter will focus primarily on applications in which fast swelling is needed andmethods for improving the rate at which materials respond to stimuli in the envi-ronment. The next section will present materials that swell from a desolvated ordehydrated state, followed by discussion of applications for environmentally sensitivematerials that swell rapidly in appropriate environments. By choosing the appropriatetechniques, one can create rapid swelling systems that can be used in both aqueousand organic environments.

FIGURE 13.1 Swelling of a hydrogel. Left: Hydrogel in a deswollen or dry state. Thepolymer chains are in close proximity and may interact with each other. As a fluid enters thehydrogel, the polymer chains undergo hydration and other interactions such as hydrophobicor electrostatic interactions. Light gray arrows indicate pressure on the system to swell. Right:When appropriate conditions are met, the hydrogel will reach a state where the polymerchains are fully extended and only the crosslinks prevent the material from dissolution. Themesh size ξ is indicated by the dark arrow.

Fast Swelling Hydrogel Systems

247

1487_book.fm Page 247 Friday, January 16, 2004 4:24 PM

POLYMER SWELLING

The thermodynamics of polymer swelling has been widely examined and has beenwell understood for several decades,27−29 but the kinetics of hydrogel swelling hasnot been as thoroughly examined. Part II of this text is dedicated to the theoreticalconsiderations of environmentally sensitive polymers and hydrogels. Of particularinterest for fast swelling materials is that the uptake of fluid into the network of thepolymer occurs while the polymer is relaxing.30 Diffusion of solvent (typically water)and solutes into the polymer network has been shown to exhibit a Fickian typediffusion, but the diffusion is retarded compared to that expected.

Diffusion has been characterized by Tanaka et al. as related to the bulk modulusK, the shear modulus µ, and the coefficient of friction ƒ between the polymer andsolvent [Equation (13.1)].30−32 Figure 13.2 represents the swelling process of apolymeric network. When dry, the polymer is placed in contact with a fluid, thefluid begins to enter the dry, solid polymer network by diffusion, and the polymerbegins to diffuse into the fluid. Over time, the polymer relaxes and reaches equilib-rium with the fluid and an interface is formed between the dry and swollen hydrogel.When all the fluid has been absorbed or the hydrogel reaches chemical equilibriumwith the fluid, a single interface is again achieved between the hydrogel and the fluid.

Tanaka and Filmore32 established a theory for swelling of hydrogels that presentsa parameter that has been used to describe the kinetics of transport of fluid intoswelling materials [Equation (13.2)]. In this relationship the characteristic time forswelling τ is related to the characteristic length of the gel a and the diffusioncoefficient D of the network.

(13.1)

(13.2)

FIGURE 13.2 Movement of fluid into a crosslinked polymer. (a) When a hydrogel (dark)and fluid (clear) are placed in proximity, the fluid diffuses into the hydrogel and the polymerchains begin to relax and diffuse into the fluid. At an intermediate point (b) between the dry(a) and fully swollen (c) states, the system will contain three distinct phases: dry hydrogel,swollen hydrogel with fluid, and fluid. Two interfaces are present: swollen hydrogel−dryhydrogel and swollen hydrogel−fluid.

(a) (b) (c)

DK

f=

+43µ

τ =a

D

2

248

Reflexive Polymers and Hydrogels

1487_book.fm Page 248 Friday, January 16, 2004 4:24 PM

This descriptor of swelling is not without some criticism. Additional studiesfrom this laboratory30,31 and others33−36 have further developed the kinetics of swell-ing of polymers in a good solvent. What is most important in these discussions isthat the fact that the characteristic length of the polymer is directly related to theswelling time is not in dispute. This suggests that large polymeric networks willrespond significantly slower than smaller polymeric networks. For this reason, reduc-ing the size of the polymeric network has been chosen as the primary method ofreducing the time for environmental response or for swelling from the dry state.26

Others have suggested that an alternative to producing smaller systems is introducinga method of rapid mass transport into the polymer networks.

IDEAS FOR RAPID SWELLING

A few methods have been proposed to increase the swelling rate for polymericnetworks. Reduction of the size of hydrogels was the first and most utilized methodto reduce the swelling time as we stated earlier.7,30−32 Several investigators havesuggested using graft polymers (Figure 13.3) to increase the sensitivity of thepolymer network and allow rapid transport in the hydrogels.37,38 This idea workswell for materials that rapidly deswell, but has not been nearly as successful formaterials that must swell since the kinetics of diffusion through the hydrogel islimiting.

A comb-type grafted poly(N-isopropylacrylamide) (nIPAAm) hydrogel was syn-thesized by Okana and coworkers.39 The comb-type hydrogel had the same chemicalcomposition but a different architecture from normal-type hydrogels and exhibitedfast deswelling kinetics responding to changes of temperature. The N-isopropylacry-lamide (nIPAAm) monomer chains were grafted to the nIPAAm backbone in thepresence of a crosslinker. The backbone and graft chains cooperatively aggregatedduring dehydration and excluded the entrapped water in 20 min. The swellingkinetics of the grafted hydrogel remained low (800 min) because mass transport intothe dehydrated system is predominantly diffusive/relaxive in nature.37,40 Increasingthe porosity of the hydrogels to enlarge the contact area between the hydrogel andthe fluid has been achieved by freeze-drying and porogen techniques.41,42

Microporous materials swell at a much faster rate than the equivalent nonporousmaterials, but do not swell with sufficient speed for many uses in which diffusion

FIGURE 13.3 Alternating and graft copolymers. In the alternating copolymer (left), the twomonomers (black and gray) are both in the polymer backbone. In the graft copolymer (right),the polymer backbone has only one monomer (black) and the grafts are repeating units ofthe copolymer (gray).

Fast Swelling Hydrogel Systems

249

1487_book.fm Page 249 Friday, January 16, 2004 4:24 PM

distances are large. This is due to the fact that the porous structure is not intercon-nected in a manner that allows fluid transport to be convective in nature.

SUPERPOROUS HYDROGELS

Superporous hydrogels (SPHs) are a new generation of hydrogels with pore size inthe range of 100 µm or larger; the mesh size of a conventional hydrogel is below100 nm.43,44 The most remarkable property of superporous hydrogels is their fastswelling ability. The swelling kinetics of SPHs is a few minutes much faster thanthat of conventional hydrogels. It usually takes hours to days for conventional hydro-gels to swell to equilibrium when their dimensions are on the order of centimeters.Rapid swelling of SPHs is due to the interconnected pore networks that are formed.45

Gas blowing techniques are used to synthesize superporous hydrogels. Controlof foaming and polymerization is necessary to form homogeneous open capillarychannels in SPHs.45 The commonly used foaming agents are inorganic carbonatessuch as Na2CO3 and NaHCO3 which have been safely applied in drug deliverysystems. Carbon dioxide gas bubbles are generated by the reaction of Na2CO3 orNaHCO3 with acid. Other methods may also be utilized as the formation of an SPHis similar to the process of forming Styrofoam.

FACTORS AFFECTING SYNTHESIS OF SUPERPOROUS HYDROGEL

The major differences in methods of preparing superporous hydrogels and conven-tional hydrogels are the additions of foaming agents and foam stabilizers to themonomer solutions. The pore size of an SPH is largely determined by the amountof gas blowing. It is essential to synchronize the foaming and the polymerizationprocesses to make homogeneous superporous hydrogels. Foam stabilizers are sur-factants that stabilize the gas bubbles produced so that the gas bubbles are sustainedfor a long period. Many surfactants have been shown to allow gas generated duringpolymerization to enable interconnected pores.43

The formation of pores on the surface of an SPH is also affected by the surfaceof the polymerization vessel.45 Polymerization vessels were modified with varioussilane molecules of varying polarity and ionic content. Hydrophobic surfaces pro-duced porous surface structures while hydrophilic surfaces produced nonporous sur-faces. Gas bubbles have a tendency to close off on the hydrophilic surface of apolymerization vessel. Surprisingly, no great difference was noted for SPHs producedin various polymerization vessels despite obvious surface morphology differences.45

This can be explained by the interconnection of pores along the axis of gas formation.The drying process also contributes to the properties of SPHs. When there is no

closing or collapse of the pore structure during drying, the swelling kinetics andswelling ratio will be maintained. Methods such as organic solvent drying (e.g., withethanol or acetone) and freeze drying are better than direct air drying. During airdrying, pores in SPHs collapse as water is removed. In contrast, organic solventshave lower surface tension than water, leaving capillary channels intact after evap-oration.43,46,47 One can maintain the interconnected pore structure under appropriateconditions, even when the SPH has been reduced in size.47 It was found that by

250

Reflexive Polymers and Hydrogels

1487_book.fm Page 250 Friday, January 16, 2004 4:24 PM

maintaining the interconnectivity of the pores, the swelling kinetics were onlymarginally reduced, despite a dramatic (up to 83%) reduction in the dry volumes ofthe hydrogels. This increased the overall volume swelling ratios of the hydrogelswithout changing the mass swelling ratios, while only increasing the equilibriumswelling time slightly (2 vs. 10 min).

Scanning electron microscopy (SEM) is a typical method to examine the mor-phology of dried samples of porous hydrogels. Many investigators examine hydro-gels under dehydrated conditions and note that they have fine porous structures thatare typically artifacts of drying processes such as freeze-drying. Upon placement influid, the polymer network hydrates and no longer contains pores.

CryoSEM techniques have shown that superporous hydrogels have extensiveopen capillary channels interconnected with each other even when hydrated.48 SPHsswollen in various solutions with varying pH levels exhibit dramatically differentpore dimensions as illustrated in Figure 13.4. Open pore structures can be noted inall pH conditions. No fine structures can be seen in these images since the polymer−water network is complete. Upon removal of water by warming the samples (similarto freeze-drying), a lacy structure can be seen in the network areas via cryoSEM(data not shown). This is due to the collapse of the polymer network and is an artifactof the SEM methodology.

SWELLING KINETICS OF SPHS

The swelling kinetics of SPHs is much faster than that of conventional (nonporous,microporous, and macroporous) hydrogels. SPHs swell to equilibrium size in min-utes, while it takes hours or days for conventional hydrogels of equal size to swellto equilibrium. This difference of swelling can be interpreted based on the morphol-ogy of these two types of hydrogels. Since the mesh sizes of conventional hydrogelsare very small (~10 nm) and mostly closed, the swelling process is predominantlydetermined by water diffusion through the glassy polymer matrix.

SPHs have very large pore sizes (100 µm to 300 µm) and extensive intercon-nected capillary channels that make their surfaces accessible to water through cap-illary effects [Equation (13.3)]. In this equation, the rate of fluid uptake δl/δt isrelated to the diameter of the capillary d, surface tension of the liquid γl, contactangle between hydrogel and fluid θ, and viscosity of the solution η.49 The porestructures of SPHs are not completely straight,45 but it has been stated that evenunder constricted pore conditions, the general form of this equation holds.50

Capillary rise is much faster than the diffusion process, and it can be calculatedfor materials with low contact angles. The typical time for a 1-cm rise of fluid in anarrow capillary (~100 µm) would be on the order of milliseconds.48 Followingcapillary rise, diffusion into the polymer network from the pores must then takeplace. The diffusive part of fluid transport is similar to the process for conventionalhydrogels, but much shorter diffusion distances are present because of the relativelysmall volume of polymer network in the total volume of the hydrogel.

(13.3)∂∂

=l

t

d

llγ θηcos

8

Fast Swelling Hydrogel Systems

251

1487_book.fm Page 251 Friday, January 16, 2004 4:24 PM

Based on Equation (13.3), the viscosity of the fluid in which a material is swollenhas an impact upon the swelling rates of SPHs. For solutions with equivalent ioniccontents and ionic strengths and varying viscosities, the swelling rates of SPHs varydramatically with viscosity (Figure 13.5). The equilibrium swelling times vary fromseconds for low viscosity conditions to hours for higher viscosity solutions. Theeffect of viscosity on the fluid also plays a part in the diffusional process [Equation(13.4)].31 The frictional component of diffusion in the polymeric network is relatedto the viscosity of the solutions and inversely related to the square of the mesh sizeof the network. The cooperative diffusion coefficient is related to the friction coef-ficient by Equation (13.1). This suggests that the change in viscosity plays a role inboth the diffusional and convective transport of the fluid in the porous network, butvisual observation attests to the fact that the convective transport of fluid in thehydrogels is significantly slower when viscosity is increased.

(13.4)

FIGURE 13.4 Scanning electron micrographs of swollen SPHs immersed in buffer solutionsof pH 2 (a), 3 (b), 4 (c), 4.5 (d), 5.0 (e), and 7.4 (f) for at least 1 day and examined usingcryoSEM. The micrographs were taken at 15× magnification. The scale bar represents 1 mm.

f ∝ηξ2

252

Reflexive Polymers and Hydrogels

1487_book.fm Page 252 Friday, January 16, 2004 4:24 PM

Theoretical analysis and observation were not in perfect agreement in this case.Despite the imperfect fit to capillary rise, the idea that capillary uptake of fluidincreases the rate of swelling of SPHs cannot be disputed. Better models that takeinto account that constricted pore structure may yield a better comparison betweentheoretical analysis and experimental observation.

ENVIRONMENTALLY SENSITIVE SPHS

Poly(acrylamide-co-acrylic acid) (pAM-AA) SPHs are pH-sensitive and fast swell-ing.51 They can swell or collapse with changes of environmental pH due to thepresence of carboxyl groups in the polymers. SPHs swollen at a pH of 1.2 and thentransferred to a pH of 7.5 swell significantly faster than nonporous hydrogels ofsimilar dimensions. Repeated swelling and deswelling were observed (Figure 13.6).The SPHs swelled at pH 7.5 and then shrank at pH 1.2 in approximately 1 min ineither direction; this compared to hours for a similar sized nonporous hydrogel ofequivalent composition. CryoSEM studies showed that pore size varied substantiallywhile the SPHs were still hydrated and maintained at various pHs (Figure 13.7).The pore diameter was nearly constant while the pH was raised from 2 to 4, but

FIGURE 13.5 Dynamic swelling ratios (q) of superporous hydrogels swollen in sucrosesolutions in PBS ranging from 50 through 900 mg/mL (n = 3) The contact angle between thehydrogel and solution was not statistically significant for the different solutions. For eachsucrose concentration (mg/mL), the viscosity η (cP) is also presented.

90

80

70

60

50

40

30

20

10

0

q

0 5 10 15 20

Time (min)

50 mg/mL − 1.04 cP300 mg/mL − 2.22 cP

100 mg/mL − 1.22 cP400 mg/mL − 3.33 cP700 mg/mL − 11.05 cP

200 mg/mL − 1.49 cP500 mg/mL − 4.96 cP800 mg/mL − 16.48 cP600 mg/mL − 7.40 cP

900 mg/mL − 24.58 cP

Fast Swelling Hydrogel Systems

253

1487_book.fm Page 253 Friday, January 16, 2004 4:24 PM

increased dramatically when raised from 4 to 7.4. This was not unexpected sincethe pKa of acrylic acid is approximately 4.5.

Poly(n-isopropylacrylamide-co-acrylamide) [p(nIPAAm-AM)] SPHs are tem-perature-sensitive and have been shown to exhibit rapid swelling characteristics.44

They showed fast swelling and deswelling kinetics when transferred repeatedlybetween fluids maintained at 10°C and 65°C. They shrank at 65°C from 36 cm3 to6.5 cm3 in 72 ± 14 s and swelled to 36 cm3 again when transferred back to 10°C in78 ± 15 s. The conventional hydrogel did not swell appreciably in 90 s. The lowercritical solution temperature (LCST) of the poly(NIPAM-AM) SPHs used in this

FIGURE 13.6 Swelling of poly(acrylic acid-co-acrylamide) SPH in simulated gastric fluid(SGF; pH, ~1.2) and simulated intestinal fluid (SIF; pH, ~7.5). The SPHs were removed fromone solution and inserted in the other solution at the times indicated by the lines (n = 3).(From Gemeinhart, R.A. et al., J. Biomater. Sci. Polym. Ed., 11, 1371, 2000. With permission.)

FIGURE 13.7 Pore diameters of swollen poly(acrylic acid-co-acrylamide) SPHs in buffersat different pH levels and equivalent ionic strengths (n = 3).

90

80

70

60

50

40

30

20

10

0

q

150 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Time (min)

1.2 7.5 1.2 7.5 1.2 7.5 1.2pH pH pH pH pH pH pH

200

100

0

pH

300

Por

e D

iam

eter

(µm

)

700

600

500

400

Dried 2.0 3.0 4.0 4.5 6.0 7.4

254 Reflexive Polymers and Hydrogels

1487_book.fm Page 254 Friday, January 16, 2004 4:24 PM

experiment was determined to be 42°C; this can be controlled by the exact polymercomposition as is true with conventional hydrogels.52 These types of hydrogels havebeen shown to rapidly respond to their environment in a fashion significantly dif-ferent from other types of hydrogels. The interconnected pores allow for convectivemass transport exterior to the polymer network, thus reduced swelling and deswellingtimes.

SUMMARY

Many types of hydrogels have been produced in the last half century, but no materialhas been produced with swelling characteristics similar to the superporous hydrogelsdeveloped by Park and coworkers.43−45,47,51 These materials are capable of rapidswelling from a dehydrated state even when the pore structure is mechanicallyreduced. Attempts to use other methods of creating porous networks have failed toachieve the rapid swelling possible in SPHs because the porous structures are notpresent.

Polymer modifications, such as graft copolymers, are insufficient to overcomethe slow response due to diffusional limitations as well as polymer relaxation, whichis kinetically slow. We have presented basic analyses of hydrogel swelling and someof the methods various investigators have used to increase the swelling and envi-ronmental swelling rates for hydrogels. Finally, we presented the concepts of super-porous hydrogel production and their use as environmental-sensitive systems.

FUTURE CONSIDERATIONS

Fast swelling hydrogels are being investigated for many biomedical and technologyapplications. When a material with a large initial and final volume is needed,superporous hydrogels and other hydrogels with large interconnected pores becomeof particular interest. These materials utilize capillary uptake of fluid that is muchmore rapid than the diffusion−relaxation phenomena that predominate in nonporoushydrogels. Care must be taken, however, as the mechanical properties of poroushydrogels can be significantly lower than nonporous hydrogels. Methods for improv-ing this quality of porous hydrogels is of particular interest, but must be balancedwith ability to swell significantly and rapidly.

Many applications, such as nanoactuators,22,23, 25,53 do not need the large volumesneeded for applications such as gastric retention drug delivery devices. The smallsize allows for sensing even when a porous network is not present. In these appli-cations, the pores would also allow transport of the fluid being analyzed when notdesired. For this reason, conventional nonporous hydrogels are optimal, but possiblemodifications such as graft copolymerization may be desired to increase sensitivity.Care must be taken when determining the type of material desired for a particularapplication. New ideas, including composite materials, may allow for future mate-rials to be even more sensitive to the external environment, but mass transfer limi-tations create a need for porous materials when rapid swelling is needed for a largevolume of material.

Fast Swelling Hydrogel Systems 255

1487_book.fm Page 255 Friday, January 16, 2004 4:24 PM

REFERENCES

1. Masuda, F., Trends in the development of superabsorbent polymers for diapers, inSuperabsorbent Polymers, F.L. Buchholtz and N.A. Peppas, Eds., Chemical Society,Washington, D.C., 1994, pp. 88–98.

2. Wichterle, O. and D. Lim, Hydrophilic gels for biological use, Nature, 185, 117, 1960.3. Matsumaru, Y. et al., Embolic materials for endovascular treatment of cerebral lesions,

J. Biomater. Sci. Polym. Ed., 8, 555, 1997.4. Cummings, J., Microspheres as a drug delivery system in cancer therapy, Expert

Opin. Ther. Patents, 8, 153, 1998.5. Park, H. and J.R. Robinson, Mechanisms of mucoadhesion of poly(acrylic acid)

hydrogels, Pharm. Res., 4, 457, 1987.6. Lowman, A.M. et al., Oral delivery of insulin using pH-responsive complexation gels,

J. Pharm. Sci., 88, 933, 1999.7. Tanaka, T., Collapse of gels and critical endpoint, Phys. Rev. Lett., 40, 820, 1978.8. Frank, S. and P.C. Lauterbur, Voltage-sensitive magnetic gels as magnetic resonance

monitoring agents, Nature, 363, 334, 1993.9. Osada, Y., H. Okuzaki, and H. Hori, A polymer gel with electrically driven motility,

Nature, 355, 242, 1992.10. Shiga, T. et al., Electric field-associated deformation of polyelectrolyte gel near a

phase transition point, J. Appl. Poly. Sci., 46, 635, 1992.11. Mamada, A. et al., Photoinduced phase transition of gels, Macromolecules, 23, 1517,

1990.12. Suzuki, A., T. Ishii, and Y. Maruyama, Optical switching in polymer gels, J. Appl.

Phys., 80, 131, 1996.13. Suzuki, A. and T. Tanaka, Phase transition in polymer gels induced by visible light,

Nature, 346, 345, 1990.14. Andreopoulos, F.M., E.J. Beckman, and A.J. Russell, Light-induced tailoring of PEG-

hydrogel properties, Biomaterials, 19, 1343, 1998.15. Zhong, X., Y.X. Wang, and S.C. Wang, Pressure dependence of the volume phase-

transition of temperature-sensitive gels, Chem. Engr. Sci., 51, 3235, 1996.16. Lee, K.K. et al., Pressure-dependent phase transition in hydrogels, Chem. Engr. Sci.,

45, 766, 1990.17. Byrne, M.E., K. Park, and N.A. Peppas, Molecular imprinting within hydrogels, Adv.

Drug Del. Rev., 54, 149, 2002.18. Peppas, N.A. and Y. Huang, Polymers and gels as molecular recognition agents,

Pharm. Res., 19, 578, 2002.19. Watanabe, M. et al., Molecular specific swelling change of hydrogels in accordance

with the concentration of guest molecules, J. Amer. Chem. Soc., 120, 5577, 1998.20. Miyata, T. et al., Preparation of poly(2-glucosyloxyethyl methacrylate) concanavalin:

a complex hydrogel and its glucose sensitivity, Macromol. Chem. Phys., 197, 1135,1996.

21. Miyata, T., N. Asami, and T. Uragami, Preparation of an antigen-sensitive hydrogelusing antigen−antibody bindings, Macromolecules, 32, 2082, 1999.

22. Van Der Linden, H. et al., Development of stimulus-sensitive hydrogels suitable foractuators and sensors in microanalytical devices, Sens. Mater., 14, 129, 2002.

23. Strong, Z.A., A.W. Wang, and C.F. McConaghy, Hydrogel-actuated capacitive trans-ducer for wireless biosensors, Biomed. Microdevices, 4, 97, 2002.

24. Chatterjee, A.N. et al., Mathematical modeling and simulation of dissolvable hydro-gels, J. Aerosp. Eng., 16, 55, 2003.

256 Reflexive Polymers and Hydrogels

1487_book.fm Page 256 Friday, January 16, 2004 4:24 PM

25. Van Der Linden, H.J. et al., Stimulus-sensitive hydrogels and their applications inchemical (micro)analysis, Analyst, 128, 325, 2003.

26. Qiu, Y. and K. Park, Environment-sensitive hydrogels for drug delivery, Adv. DrugDeliv. Rev., 53, 321, 2001.

27. Flory, P.J., Principles in Polymer Chemistry, Cornell University Press, Ithaca, NY,1953.

28. Mikos, A.G. and N.A. Peppas, Flory interaction parameter chi for hydrophilic copol-ymers with water, Biomaterials, 10, 95, 1988.

29. Kumagai, H., A. Mizuno, and T. Yano, Analysis of water sorption isotherms ofsuperabsorbent polymers by solution thermodynamics, Biosci. Biotechnol. Biochem.,61, 936, 1997.

30. Li, Y. and T. Tanaka, Kinetics of swelling and shrinking of gels, J. Chem. Phys., 92,1365, 1990.

31. Tokita, M. and T. Tanaka, Friction coefficient of polymer networks of gels, J. Chem.Phys., 95, 4613, 1991.

32. Tanaka, T. and D.J. Fillmore, Kinetics of swelling gels, J. Chem. Phys., 70, 1214,1970.

33. Hakiki, A. and J.E. Herz, A study of the kinetics of swelling in cylindrical polystyrenegels: mechanical behavior and final properties after swelling, J. Chem. Phys., 101,9054, 1994.

34. Tomari, T. and M. Doi, Swelling dynamics of a gel undergoing volume transition,J. Phys. Soc. Jpn., 63, 2093, 1994.

35. Barriere, B. and L. Leibler, Kinetics of solvent absorption and permeation through ahighly swellable elastomeric network, J. Polym. Sci. B Polym. Phys., 41, 166, 2003.

36. Peters, A. and S.J. Candau, Kinetics of swelling of spherical and cylindrical gels,Macromolecules, 21, 2278, 1988.

37. Annaka, M. et al., Transport properties of comb-type grafted and normal-type n-iso-propylacrylamide hydrogel, Langmuir, 18, 7377, 2002.

38. Lu, S.J., M.L. Duan, and S.B. Lin, Synthesis of superabsorbent starch graft−poly(potassium acrylate-co-acrylamide) and its properties, J. Appl. Polym. Sci., 88,1536, 2003.

39. Kaneko, Y. et al., Influence of freely mobile grafted chain length on dynamic prop-erties of comb-type grafted poly(n-isopropylacrylamide) hydrogels, Macromolecules,28, 7717, 1995.

40. Annaka, M. et al., Fluorescence study on the swelling behavior of comb-type graftedpoly(n-isopropylacrylamide) hydrogels, Macromolecules, 35, 8173, 2002.

41. Serizawa, T. et al., Thermoresponsive properties of porous poly(n-isopropylacryla-mide) hydrogels prepared in the presence of nanosized silica particles and subsequentacid treatment, J. Polym. Sci. Pol. Chem., 40, 4228, 2002.

42. Omidian, H. and M.J. Zohuriaan-Mehr, Dsc studies on synthesis of superabsorbenthydrogels, Polymer, 43, 269, 2002.

43. Chen, J., H. Park, and K. Park, Synthesis of superporous hydrogels: hydrogels withfast swelling and superabsorbent properties, J. Biomed. Mater. Res., 44, 53, 1999.

44. Chen, J. and K. Park, Superporous hydrogels: Fast responsive hydrogel systems,J. Macromol. Sci Pure Appl. Chem., A36, 917, 1999.

45. Gemeinhart, R.A., H. Park, and K. Park, Pore structure of superporous hydrogels,Polym. Adv. Technol., 11, 617, 2000.

46. Dorkoosh, F.A. et al., Preparation and NMR characterization of superporous hydro-gels (SPH) and SPH composites, Polymer, 41, 8213, 2000.

Fast Swelling Hydrogel Systems 257

1487_book.fm Page 257 Friday, January 16, 2004 4:24 PM

47. Gemeinhart, R.A., H. Park, and K. Park, Effect of compression on fast swelling ofpoly(acrylamide-co-acrylic acid) superporous hydrogels, J. Biomed. Mater. Res., 55,54, 2001.

48. Gemeinhart, R.A., Properties of Superporous Hydrogels for Drug Delivery, Ph.D.thesis, Purdue University, West Lafayette, IN, 1999.

49. Lightfoot, E.N., Transport Phenomena and Living Systems: Biomedical Aspects ofMomentum and Mass Transport, John Wiley & Sons, New York, 1974.

50. Sharma, R. and D.S. Ross, Kinetics of liquid penetration into periodically constrictedcapillaries, J. Chem. Soc. Faraday Trans., 87, 619, 1991.

51. Gemeinhart, R.A. et al., pH-sensitivity of fast responsive superporous hydrogels,J. Biomater. Sci. Polym. Ed., 11, 1371, 2000.

52. Kabra, B.G. and S.H. Gehrke, Synthesis of fast response, temperature-sensitivepoly(isopropylacrylamide) gel, Polymer Commun., 32, 322, 1991.

53. Selic, E. and W. Borchard, A new apparatus for the characterization of the swellingbehavior of micro-gel particles, Macromol. Chem. Phys., 202, 516, 2001.