Introduction

         We report the macromolecular release from nanocomposite hydrogels. Poly(NIPAm) cross-linked with either N,N′-methylenebisacrylamide (MBAm), N,N′-cystaminebisacrylamide (CBAm), or both serves as the polymer matrix. Gold nanostructures are then synthesized within the hydrogel matrix. The physicochemical properties, including equilibrium swelling and phase transition behavior, of these composite materials has been reported.¹ Notably, the introduction of gold into hydrogels containing the CBAm cross-linker results in significant increases in equilibrium swelling mass and the temperature at which the hydrogel deswells. This work investigates the temperature-dependent release from these composite materials and their counterparts lacking gold nanostructures, referred to as native hydrogels. Five molecules—diltiazem HCl (DHCl), vitamin B12 (VB12), and three different molecular weight dextrans (3, 10, and 40 kDa) labeled with tetramethylrhodamine (D3a, D10n, and D40n)—serve as probes for investigating the release behavior.

Results

Molecular Weight. The effect of molecular weight on the release pattern from a 0.00M/3.50C hydrogel containing gold nanostructures is shown in Figure 1. Here an increase in release rate is seen moving from the highest molecular weight macromolecule D40n to the lowest DHCl. This pattern is observed for most hydrogels when release data is collected at 25 °C.

Temperature. Temperature influences release rate of macromolecules from the hydrogel matrices. For all native hydrogels and for the 3.50M/0.00C hydrogel containing gold nanostructures nearly complete cessation of release is observed at 35 and 40 °C. When gold is introduced into CBAm cross-linked poly(NIPAm) hydrogels, however, the higher temperatures do not stop release from the hydrogel. The continued release at elevated temperatures is most pronounced for the 0.00M/3.50C hydrogels carrying lower molecular weight macromolecules. This behavior correlates with the increased phase transition temperatures observed for the CBAm cross-linked hydrogels after gold introduction.¹

Release Mechanism. Analysis of the release profile can be performed to determine the release mechanism.^2,3 Here data were fit to the function:

F = ktⁿ                                                                      (1)

where F is the fractional release, k is the release constant, and n is the diffusional exponent. For matrix (Fickian) diffusion, n is generally assumed to have a value of 0.50, but 0.45 has been argued as a better approximation for hydrogels of the geometry used here.^2,3

All data were fit to the power law described in equation (1). Results from this analysis yielded n values ranging from 0.12 to 0.65. Larger values are observed with the lower molecular weight macromolecules with DHCl and VB12 possessing average values of 0.50 and 0.43, respectively. Higher molecular weight species have lower n values, with D10n and D40n at 0.23 and 0.22, respectively. These values are clearly below that predicted for Fickian release. The reduction in n with increasing molecular weight of the macromolecule has been observed in other work using poly(NIPAm) hydrogels, where a value of 0.275 was obtained for D40n.⁴ We believe that this deviation likely results from rapid release of macromolecules near the surface of the hydrogel.

Participation of and Outcomes for Student Researchers

Five Wellesley College students participated in the research supported by the ACS-PRF grant, including two student-summers of support. Four of these students have presented results at National Meetings of the ACS. All of these students are expected to be co-authors on one of two manuscripts describing the results of these studies, which will be submitted within the 2007 calendar year. Future work within my group will extend the studies to analogous systems.

References

(1)        Pong, F. Y.; Lee, M.; Bell, J. R.; Flynn, N. T. Langmuir 2006, 22, 3851-3857.

(2)        Ritger, P. L.; Peppas, N. A. J. Controlled Release 1987, 5, 37-42.

(3)        Ritger, P. L.; Peppas, N. A. J. Controlled Release 1987, 5, 23-36.

(4)        Coughlan, D. C.; Quilty, F. P.; Corrigan, O. I. J. Controlled Release 2004, 98, 97-114.