From Polymer Gel Nanoparticles to Nanostructured Bulk Gels

Zhibing Hu

Departments of Physics and Chemistry, University of North Texas

Denton, TX 76203, U. S. A. Phone: 940-565-4583, FAX: 940-565-4824, e-mail: zbhu@unt.edu

This brief review will cover recent progresses in our group for the development of a class of nanostructured hydrogels.[1-6] The central idea is to first synthesize monodispersed hydrogel nanoparticles, then self-assemble them into a network, and covalently bond neighboring particles. The covalent bonding contributes to the structural stability, while self-assembling provides crystal structures that diffract light, resulting in a striking iridescence like opal. Self-assembling behavior of N-isopropylacrylamide (PNIPAM) nanoparticles in water as a model system has been studied in room temperature using light scattering and turbidity methods.[3] Two batches of NIPA microgel spheres were synthesized with their hydrodynamic radii of 132 and 216 nm in water at 25 °C. The concentrations ranging from ~ 0.01 wt% to ~ 14 wt% were obtained by dilution/condensation of the dispersions. As polymer concentration increases, the microgel spheres in dispersions exhibit the liquid, the crystal and the glass states, while the optical appearance of the dispersions changes from transparent to cloudy, then to colored (pink, green, blue and purple gradually), and eventually to transparent. The formation of large colloidal crystals in a very narrow concentration range (ca. 3~5 wt%), at room temperature (18 ~ 22 °C), yields iridescent patterns from typical Bragg diffraction. For a colored dispersion, the turbidity as the function of wavelength λ exhibits a sharp shoulder-shape increase at a certain λc with decreasing wavelength. It is found that λc shifts linearly to a lower wavelength with the decrease of inter-particle distance.

The temperature dependent self-assembling behavior of PNIPAM nanoparticles dispersed in water is investigated using thermodynamic perturbation theory combined with light scattering and spectrometer measurements. [4-5] It is shown that the volume transition of PNIPAM particles affects the interaction potential and determines a novel phase diagram that has not been observed in hard-sphere-like colloidal dispersions. Because both particle size and attractive potential depend on temperature, a PNIPAM aqueous dispersion exhibits phase transitions at a fixed particle density by either increasing or decreasing temperature. The phase behavior of nanoparticle dispersion resembles that for hard spheres at temperatures below the volume transition temperature. However, at higher temperatures, the phase separation is obtained, driven by van der Waals attractions.

We have proposed to synthesize bulk gels by covalently bonding self-assembled gel nanoparticles.[1-2] Such a nanostructured polymer gel should have a two-level structural hierarchy: the primary network consists of crosslinked polymer chains inside each nanoparticle, while the secondary network is a crosslinked system of the nanoparticles. The mesh sizes of the primary and the secondary networks are typically around 1-10 nm and 10-500 nm respectively. However, it is difficult to measure gel nanoparticle networks with electron microscope techniques, since the inherent nanoparticle network structure cannot be preserved during the sample preparation steps either by critical drying or freezing-dry methods. The rapid freezing of the water swollen gel and the subsequent fast evaporation in a vacuum often leads to the collapse

of the pore structure due to ice crystal formation. To test the structure of a nanoparticle network, we have first attached vinyl groups on hydroxypropylcellulose (HPC) polymers.[6] The vinyl groups allowed for chemical linking of the HPC chains into nanoparticles through a free radical polymerization process above its low critical solution temperature (LCST). The residual vinyl groups on the terminus of attached functional groups on the exterior of the nanoparticles have been further linked together to form the nanoparticle network. The controlled release of biomolecules from this network was correlated with the primary structure that comprised crosslinked polymer chains in each individual particle and the secondary structure that was a system of crosslinked nanoparticles. References [1] Hu, Z. B.; Lu, X. H.; Gao, J.; Wang, C. J. Advanced Materials 2000, 12, 1173. [2] Hu, Z. B.; Lu, X. H.; Gao, J. Advanced Materials 2001, 13, 1708. [3] Gao, J.; Hu, Z. B. Langmuir 2002, 18, 1360. [4] Wu, J. Z.; Zhou, B.; Hu, Z. B. Phys. Rev. Lett. 2003, 90, 048304. [5] Wu, J. Z.; Huang, G.; Hu, Z. B. Macromolecules 2003, 36, 440. [6] Cai, T.; Hu, Z. B.; Ponder, B.; John, J. V.; Moro, D. Macromolecules 2003, 36, 6559.

From Polymer Gel Nanoparticles to Nanostructured Bulk Gels

Zhibing Hu

Departments of Physics, Chemistry and Materials Science

University of North TexasDenton, TX 76203

Bulk gels and nanostructured bulk gels

Bulk gelsMicrogels (1 µm-1000 µm)Gel nanoparticles (100 nm-1µm)Gel nanoparticle networks--Nanostructured bulk gels

Conceptual model: A nanostructured bulk gel consists of covalently bonded gel nanoparticles. It could have a randomly packed structure or a periodic structure.

The left figure is adapted from Ref. 1.

Hydrodynamic radius distributions (f(Rh)) of Poly-N-isopropylacrylamide PNIPAM microgel spheres in water at T = 25.0 oC (circle) and 40.0 oC (square), respectively, where C = 1.37 × 10–5 g/g. The figure is adapted from Ref. 2.

Zimm plot of PNIPAM gel particles in water at 25.0 oC, where polymer concentration ranges from 8.75 ×10 –7 to 4.2 × 10 –6 g/g. The figure is adapted from Ref. 2.

Dynamic and static light scattering results of PNIPAM nanoparticles in water

T (oC)

<Rh> (nm)

<Rg>(nm)

<Rg>/<Rh> Mw (108g/mol)

ρ (g/cm3)

B2

(10-5 mol mL/g2)

25 132 87 0.66 1.5 0.026 7.6

40 49.8 38 0.76 1.4 0.45 -3.5

PNIPAM nanoparticle dispersions at 21 oC with different concentrations (C): A (0.064), B (1.47), C (3.0), D (3.4), E (4.2), F (4.6), G (5.95), H (7.92), I (13.7 wt%). The figure is adapted from Ref. 2.

B ACDEFI H G F E D C B A

Schematic “phase diagram” of PNIPAM nanoparticle

water dispersions. The figure is adapted from Ref. 2.

The turbidity curves with a peak from left to right correspond to C=4.47x10-2, 3.65x10-2, and 3.21x10-2 g/g. The curve without a peak corresponds to C= 1.99x10-2 g/g. The figure is adapted from Ref. 2.

Linear fitting: Bragg condition 2ndsinθ = mλ at θ = 90 °, slope = 2.04

The figure is adapted from Ref. 2.

Temperature dependent phase behavior of a PNIPAM nanoparticle dispersion with a polymer concentration of 16.9 g/L: a) 21oC, b) 26oC, c) 35oCThe figure is adapted from Ref. 3.

Reduced osmotic second virial coefficient (B2) from the static light scattering (symbols) and from the calculation. The figure is adapted from Ref. 3.

-8

-6

-4

-2

0

2

20 25 30 35 40T ( oC )

B2/B

2HS

The potential between hydrogel nanoparticle may be effectively represented by the Sutherland-like function(Dr. J. Z. Wu, UC-Riverside)

σσ

σσσ

≥<

⎪⎩

⎪⎨⎧

⎟⎠⎞

⎜⎝⎛⎟

⎠

⎞⎜⎝

⎛−

∞=

+

rr

rTT

kTru nn6

00)(

Repulsive interaction

van der Waals-like attraction

The phase diagram of aqueous dispersions of PNIPAM particles determinedfrom turbidity measurements (symbols) and from the thermodynamicperturbation theory (lines). The figure is adapted from Ref. 4.

1 5

2 0

2 5

3 0

3 5

4 0

0 5 0 1 0 0 1 5 0 2 0 0 2 5 0 3 0 0

M ic ro g e l w e ig h t c o n c e n tra tio n (g /L )

Tem

pera

ture

(o C)

s o lutio n

flu id -flu id p ha s e tra ns i tio n

c rys ta l

Formation of hydrogel opals: two different building blocks of PNIPAM-derivative nanoparticles were synthesized

1. The N-isopropylacrylamide (PNIPAM) co-polymerized with acrylic acid (AA)

2. The PNIPAM with 2-hydroxyethyl acrylate (HEAc).

The NIPA had thermally responsive properties, while the AA and the HEAc provided carboxyl (-COOH) and hydroxyl (-OH) groups for the crosslinking sites.

Epichlorohydrin was used to bond PNIPAM-AA nanoparticles in acetone, while divinylsulfone (DVS) was use to bond PNIPAM-Heacnanoparticles in an aqueous solution (pH 12)

Scheme 1

CH2 ClCH CH2

O

NIPACHO

O

NIPA C

O

O CH2 CH CH2 O C NIPA

O

OH

Scheme 2

OH CH2 CH SO2 CH CH2 NIPAHONIPA

OH-

NIPA O NIPACH2CHSO2CHCH2O 2 2

C OH

O

NIPA

The average hydrodynamic radii for the two red samples (left) and the two green samples (right) in water at room temperature were 175 and 150 nm, respectively. The figure is adapted from Ref. 5

R=175 nm R=150 nm

3.0 3.1 3.8 4.0wt%

A PNIPAM- HEAc crystal hydrogel in a test tube is transparent and exhibited colored speckles at 21 oC until the temperature was raised to 50 oC. The figure is adapted from Ref. 5.

21 oC 50 oC

New approach: PNIPAM-allylamine nanoparticledispersions at various polymer concentrations at 23 oC.The figure is adapted from Ref. 6.

The turbidity versus wavelength curves. The Bragg diffraction peak shifts to lower wavelength as the polymer concentration increases. The figure is adapted from Ref. 6.

550 600 650

0.5

1.0

1.5

2.0

2.5

Turb

idity

(cm

-1)

Wavelength (nm)

c=3.5 wt.-% c=3.0 wt.-% c=2.5 wt.-% c=2.0 wt.-%

The phase diagram of the PNIPAM-allylaminenanoparticle dispersions The figure is adapted from Ref. 6.

2.0 2.5 3.0 3.5 4.0

15

20

25

30

35

40

Glass

Crystal

Liquid

Phase Separation

Tm Tg

T (o C

)

C (wt.-%)

The PNIPAM-allylamine crystal hydrogel changes its iridescent colors with the temperature. The diameter of the vial is 2.73 The figure is adapted from Ref. 6.

Two levels of structural hierarchy of the polymer gel nanoparticle network and controlled dug delivery

Hydrogel nanoparticle networks have two levels of structural hierarchy: the primary network is crosslinked polymer chains in each individual particle, while the secondary network is a system of crosslinked nanoparticles. The interstitial space between particles (mesh size) within the network can be adjusted by changing the particle size. This can be used to control the release rate of drugs that are entrapped between the particles

Nanoparticles of hydroxypropyl cellulose (HPC) as building blocks. The figure is adapted from Ref. 7.

OO

OOOO

O HO

HO

O

HO HO

OHHO

( (Cl

O

+O

OOOO

O

O HO

HO

O

HO HO

OHO

( (O

Dimethylacetamide, r.t., 48 h

Scheme 1

A hydroxypropylcellulose (HPC) nanoparticle network was formed with a small molecule (bromocresol green) (BCG) entrapped within the particles and a large chemical entity (BSA) entrapped between the particles

0

5

10

15

20

25

30

35

0 10 20 30 40 50 60 70

BSABCG

Mod

el C

ompo

und

Rel

ease

(%)

Time (h)

The figure is adapted from Ref. 7.

Developing hydrogel nanoparticle networks based on physical crosslinks (Dr. X. H. Xia)

Chemically crosslinked nanoparticle networks: Covalent bond, Permanent structure

Physically crosslinked nanoparticle networks: Hydrophobic interaction, Reversible structure

Synthesis of PNIPAM-PAA interpenetrating networks (IPN) nanoparticles. The IPN dispersion exhibits the inverse thermoreversible gelation.

Acknowledgments

This work is supported by NSF, ARO and Texas Advanced Technology ProgramT. Cai, Dr. J. Gao, G. Huang, Dr. X. H. LuDr. X. H. Xia, B. Zhou Prof. J. Z. Wu (UC-Riverside)Dr. J. V. John, D. Moro and B. Ponder (Access Pharmaceuticals)

Acknowledgments

Prof. Mitsuhiro ShibayamaProf. Haruma Kawaguchi

References

1. Z. B. Hu, X. H. Lu, J. Gao and C. Wang, “Polymer gel nanoparticlenetworks,” Advanced Materials 12, 1173 (2000).

2. J. Gao and Z. B. Hu, “Optical properties of N-isopropylacrylamidemicrogel spheres in water,” Langmuir 18, 1360-1367 (2002).

3. J. Z. Wu, B. Zhou and Z. B. Hu, “Phase Behavior of Thermally Responsive Microgel Colloids,” Phys. Rev. Lett. 90, 048304 (2003).

4. J. Z. Wu, G. Huang, Z. B. Hu, “Inter-particle potential and the phase behavior of temperature-sensitive microgel dispersions,”Macromolecules 36, 440 (2003). Z. B. Hu, X. H. Lu and J. Gao,

5. “Hydrogel opals,” Advanced Materials 13 (Cover), 1708 (2001). 6. Z. B. Hu and G. Huang, “A new route to crystalline hydrogels as guided

by a phase diagram,” Angewandte Chemie, Int. Ed. 42, 4799 (2003).7. T. Cai, Z. B. Hu, B. Ponder, J. V. John, and D. Moro, “Synthesis and

study of and controlled release from nanoparticles and their networks based on functionalized hydroxypropylcellulose,” Macromolecules 36, 6559-6564 (2003).