Chapter 22
pH-Sensitive Hydrogels Based on Hydroxyethyl Methacrylate and Poly(vinyl alcohol)—Methacrylate Downloaded by UNIV OF CALIFORNIA SAN DIEGO on March 3, 2016 | http://pubs.acs.org Publication Date: November 30, 1993 | doi: 10.1021/bk-1994-0540.ch022
Y. J. Wang, F. J. Liou, S. W. Tsai, and G. G. C. Niu Institute of Biomedical Engineering, National Yang-Ming Medical College, Taipei, Taiwan, Republic of China Hydrogels, derived from the copolymerization of HEMA and PVΑ -ΜΑ with low concentrations of TMPTMA, were prepared. By increasing the amount of PVA-MA in the hydrogel, the water content increased, but the mechanical strength decreased instead. The PVA -MA containing polymeric hydrogel swelled in responding to the pH changes from 3 to 7. The linear swellability can be increased either by increasing PVA-MA content or by decreasing TMPTMA concentration. While both NaCl and CaCl had little effects on the swelling, urea suppressed the pH induced gel expansion significantly. 2
Polyvinyl alcohol) (PVA) is one of the hydrogels most often used in biomaterial a p p l i c a t i o n s B e c a u s e of the presence of excessive hydroxyl groups, PVA contained a significant amount of water. PVA was also claimed to have good mechanical strength.5>6 Another hydrogel, poly(2-hydroxyethyl methacrylate) (polyHEMA), is well known for its excellent biocompatibility.7>8 The versatile biomedical applications of poly-HEMA are demonstrated by its uses in contact lenses, vitreous humor replacements and suture materials. To explore a new formulation and other usages of these two polymers, we have copolymerized HEMA with PVA-MA (PVA esterified with maleic anhydride), the preparation and properties of this copolymer are discussed in this article. Experimental Chemicals Polyvinyl alcohol), 2-hydroxyethyl methacrylate and maleic anhydride were perchased from Merck-Schuchardt (Germany). The average molecular weight of poly (vinyl alcohol) used is about 72,000. The cross-linker, 1,1,1-trimethylol propane trimethacrylate; and initiator, 2,2-diethoxyacetophenone, were obtained from TCI (Kasei, Tokyo, Japan). All chemicals used in this experiment are of reagent grade. PVA-MA Preparation. Ten grams of PVA was mixed with 22.4 g of maleic anhydride in 100 ml dimethyl sulfoxide. The esterification reaction was proceeded at 60°C with continuous stirring. After a reaction period of 1, 3, 5 or 7 hours, the
0097-6156/94/0540-0251$06.00/0 © 1994 American Chemical Society
In Polymers of Biological and Biomedical Significance; Shalaby, Shalaby W., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1993.
252
POLYMERS OF BIOLOGICAL AND BIOMEDICAL SIGNIFICANCE y
reaction product was isolated by the method similar that described by Chiang et al. Briefly, the resulted PVA-MA was purified by repeated solubilization in methanol and precipitation in acetone. The approximated extent of esterification was calculated by using the following equation: E= m* W *72,000/W * W a
t
D
where Ε is the extent of esterification, m is the moles of NaOH needed totitratePVA-MA to the end point, W is the total weight of PVA-MA recovered after esterification, Wb is the total weight of PVA used for esterification, Wt is the weight of PVA-MA used for titration.
Downloaded by UNIV OF CALIFORNIA SAN DIEGO on March 3, 2016 | http://pubs.acs.org Publication Date: November 30, 1993 | doi: 10.1021/bk-1994-0540.ch022
a
The purified PVA-MA was dissolved in methanol and stored at 4°C until use. Thin Films of Hydrogels. Thin films of poly-HEMA, poly(HEMA-co-(PVA-MA)) and poly(PVA-MA) were prepared with compositions listed in Table 1. The crosslinking reactions of hydrogels were carried out by UV irradiation using 2,2diethoxyacetophenone as an initiator as described previously.10 The Young's modulus of the gel film was determined by the slope obtained from the plot of initial stress versus strain. The length of the gel in solution was measured by using a caliper. The expansion of the gel was represented by (L - L )/Lo, where L is the gel length at equilibrium and Lo, the original gel length. The original dimensions of the gel tested for swelling are about 1 cm long, 0.5 cm wide and 0.25 mm thick. Each sample was measured in triplicate and the standard deviation obtained was about 15 %. 0
Results and Discussion Esterification of PVA with maleic anhydride. Maleic acid has two dissociation constants with pKa values of 1.9 and 6.3. On the other hand, PVA-MA has only one pKa (3.2) with atitrationend point of pH 6.5. The extent of esterification increased from 12 % to 40 % by increasing the reaction time from 1 hour to 3 hours. Further increase in reaction time has no effect on the extent of esterification (Figure 1). A reaction period of 3 hours was therefore chosen in preparing PVA-MA. Characterization of poly(HEMA-co-(PVA-MA)) hydrogel. The IR spectra of Poly(HEMA-co-(PVA-MA)) is shown in Figure 2. A strong absorption band at 1720 cm"l, corresponding to the stretching mode of carbonyl group of ester, could be found. In addition, a broader absorption band around 3500 cm"* appeared due to the presence of carboxylic acid in PVA-MA. With a low (0.6 %) TMPTMA content, poly-HEMA contains about 70 % water. By including PVA-MA (weight ratio, PVA-MA/HEMA = 1/9) in the polymeric network, the water concentration increased to 80 %. Without the addition of HEMA, the water content of poly(PVA-MA) reached 99 %. Apparently, the ionized carboxylic acids in the polymeric network formed significant number of hydrogen bonding with water molecules. In addition, the negatively charged groups repelled each other, leaving space for water molecules in die polymeric network. This is turn, weakened the mechanical strength of the copolymer. The Young's modulus of poly-HEMA and poly(HEMA-co-(PVA-MA)) were determined to be 0.45 MPa and 0.1 MPa, respectively. The decrease in strength is not due to the effect of PVA molecule since poly(HEMA-co-(PVA-AA)) with a Young's modulus of 1.4 MPa was stronger than poly-HEMA. The existence of the negatively charged carboxyl ions in the copolymeric network structure enabled the gel to respond to pH changes. Figure 3 shows the expansion of the hydrogel in responding to pH changes. The gel wasfirstequilibrated in a citrateIn Polymers of Biological and Biomedical Significance; Shalaby, Shalaby W., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1993.
22. WANG ET AL.
253
pH-Sensitive Hydrogeh
Table 1. Compositions of Poly(HEMA), Poly(HEMA-
