Materials. 2-hydroxyethyl methacrylate (HEMA, 99%, Fluka), 2-hydroxyethyl acrylate (HEA, >97%, Fluka), ?,?

1
Copolymerization of 2-hydroxyethyl acrylate and
2-hydroxyethyl methacrylate Controlling the
water content of hydrogels
Alfonso Ramirez and W. Tandy Grubbs, Stetson
University, Department of Chemistry, Unit 8271,
DeLand, FL 32720, wgrubbs_at_stetson.edu
Results (continued)
Introduction
Results (continued)
Results
Hydrogels are polymer that are insoluble in
aqueous solution, yet they are capable of
absorbing large amounts of water.1 Hydrogels can
be found in many consumer products disposable
diapers, incontinence pads, and bandages. More
recently, hydrogels are finding use in a medical
applications.2 In particular, hydrogels based
upon 2-hydroxyethyl methacrylate (HEMA) have been
found to exhibit remarkable biocompatibility
HEMA is used to make commercial soft contact
lenses and has been studied as an artificial
tissue. Controlled drug delivery represents
one of the more promising fields of application
for HEMA hydrogels. The ability of water to
permeate, diffuse through the hydrated gels, and
carry away an imbedded drug has been demonstrated
in several case studies.3-5 Widespread
application of HEMA hydrogels as drug delivery
vehicles has not be realized because of
mechanical instabilities that arises during water
absorption.6,7 Attempts to enhance the
mechanical stability of these systems by
incorporating various cross-linkers in the
polymer formulation have led to an undesired
decrease in water absorption.6,7 An
alternate approach to preparing HEMA based
hydrogels with controlled water absorption
tendencies is presented here. HEMA is randomly
copolymerized with 2-hydroxyethyl acrylate (HEA)
the monomers associated with this work are
shown in Figure 1. Alone, the HEA homopolymer
exhibits a much higher tendency to absorb water
the percentage water absorption of HEA is nearly
600 in comparison to HEMA homopolymer which
exhibits 84 water absorption.
To perform quantitative FTIR analysis on a
copolymer formulation, one must first identify an
absorption peak that is distinct to one
homopolymer (preferably at wavenumbers higher
than 1000 cm-1) which has an isosbestic point to
each side. An inspection of Figure 4 reveals
that the C-H deformation peak at 1484 cm-1 is
amenable to such analysis (the region around this
peak is illustrated in Figure 5). This peak is
due to the CH3 group in HEMA. Integration of
the area under this peak between 1456 cm-1 and
1515 cm-1 and subtraction of the baseline
absorption of poly-HEA in this region yielded the
mole fraction of HEMA in each copolymer.
The 100 anhydrous HEMA homopolymer is
highly brittle, whereas the 100 HEA homopolymer
is elastic and sticky to touch. The mechanical
properties of the copolymers vary between these
two extremes. The mechanical stability of the
hydrogels decreases upon swelling in water, and
the degradation is more pronounced as the
percentage HEA in the copolymer increases.
Results from the percentage water absorption
measurements for the five hydrogels are
illustrated in Figure 2, revealing a marked
increase in water absorption as increasing
amounts of HEA are incorporated into the polymer.
After drying these copolymer formulations in
a vacuum oven, they are difficult to re-dissolve
in standard solvents (the samples remain
insoluble even after sonication at elevated
temperatures in DMF or DMSO). Consequently,
attempts to characterize the copolymer
composition of these polymers by traditional
solution-phase NMR and IR methods have not been
successful. We have had some preliminary
success in recording infrared spectra of these
formulations by mounting a small amount of dry
polymer (or copolymer) against an attenuated
total reflection (ATR) sampling crystal
(purchased from PIKE Technologies). The PIKE
MIRacleTM ATR sampling attachment is illustrated
below in Figure 3. Since the HEMA and HEA
monomers only differ structurally by a
CH3 group (see Figure 1), the IR spectra are
only expected to exhibit substantial spectral
differences in the C-H stretching and deformation
regions (Illustrated in Figures 4 and 5).

Figure 5 Expanded view of the C-H deformation
region. The peak at 1484 cm-1 arises from the
CH3 group in HEMA.
Figure 2 Percentage water absorption as a
function of percentage of 2-hydroxyethyl acrylate
monomer in the polymer. Error bars are standard
deviations based upon at least 3 trials. The
relative amounts of HEMA/HEA were determined by
quantitative ATR-FTIR measurements, discussed
below.
Conclusion
Figure 3 The MIRacle ATR-FTIR sampling
attachment purchased from PIKE Technologies
(www.pike.com)..
Figure 1 2-hydroxyethyl methacrylate (HEMA) and
2-hydroxyethyl acrylate (HEA) monomers
__________________________________________________
______ The percent water in most
biological tissues is approximately 80, in line
with the 84 value measured here for the HEMA
homopolymer. The results presented in Figure 1
show that the percent water absorption in
HEMA-HEA co-polymers can be tuned upward
substantially from the 80 range by incorporating
HEA into the formulation. The ability to improve
the inherent water absorption tendency of a HEMA
system will be important in biological
applications where a crosslinker has been
utilized to improve the mechanical stability of
the swollen gel. Since many crosslinkers are
hydrophobic in nature (derivatives of ethylene
glycol dimethacrylate are often used), their
incorporation in the hydrogel can cause an
undesirable decrease in water absorption
capability. This undesired effect can be offset
by including an appropriate amount of HEA in the
crosslinked HEMA hydrogel. Future studies will
address this issue. During synthesis, we
have noted that the reactivity of the HEA monomer
is about three times as fast as the HEMA monomer.
Consequently, a 50/50 (by volume) reaction
mixture of these monomers will not necessarily
give rise to equal molar amounts of the two
monomers in the final copolymer. Therefore, some
method should be employed to determine the actual
monomer composition of the products.
A series of HEMA-HEA random copolymers have
been prepared and characterized in terms of their
water absorption tendencies. Results suggest
that this system holds promise as biocompatible
hydrogel systems. Future studies will address
the effect of adding a crosslinking agent (to
improve the mechanical properties of the swollen
gel), while maintaining an approximate 80
percent water absorption in the system.
Experimental
Materials. 2-hydroxyethyl methacrylate
(HEMA, 99, Fluka), 2-hydroxyethyl acrylate (HEA,
gt97, Fluka), ?,?-azo-bis-isobutryo-nitrile
(AIBN, Kodak), tetrahydrofuran (THF, gt99,
Aldrich), and dimethylformamide (DMF, 99.8,
Aldrich). Synthesis. Hydrogels were
prepared by combining HEMA and HEA in the
reaction vessel according to the following
percentages of HEMA (by volume) 0, 25, 50, 75,
and 100 HEMA. 20 mL of DMF, 15 mL of monomer(s)
solution, and 20 mg of AIBN were combined in a
sealed flask, the solution was purged with N2 for
5 minutes, and then random polymerization was
carried out at 70 ?C until the reaction mixture
became visibly viscous. The polymer was then
precipitated in THF, and washed with several
fresh volumes of THF. The hydrogels were
subsequently dried at 40 ?C in a vacuum oven for
2 weeks. Characterization. The percentage
water absorption was determined by weighing
samples before and after soaking the polymer
samples in distilled water for 3 days. Infrared
spectroscopic investigations were carried out on
the dry hydrogels using a Perkin-Elmer Spectrum
One FTIR in conjunction with a MIRacleTM
attenuated total reflection (ATR) attachment
(PIKE Technologies).
References
1. Kopecek, J. Nature (London) 2002, 417,
388. 2. Nguyen, K. and West, J. Biomaterials
2002, 23, 4307. 3. Qiu, Y. and Park, K. Adv. Drug
Delivery Rev. 2001, 46, 125. 4. Brazel, C. and
Peppas, N. Polymer 1999, 40, 3383. 5. Peppas, N.
and Scott, R. Biomaterials 1999, 20,
1371. 6. Barnes, A., Corkhill, P. and Tighe, B.
Polymer 1988, 29, 2191. 7. Mequanint, K. and
Sheardown, H. J. Biomater. Sci. Polymer Edn.
2005, 16, 1303.
Acknowledgements
Figure 4 Comparison of ATR-FTIR spectra for the
HEMA and HEA homopolymers and the various
copolymer formulations. The ATR correction has
been applied to these spectra and each has been
normalized to the C-O stretching band at 1072
cm-1.
This work was funded in part by the National
Science foundation (DMR-0215407). Special thanks
to Amy Luce who carried out some of the
preliminary measurements in the HEMA-HEA system.