Bio-Medical Materials and Engineering 24 (2014) 1725–1733 DOI 10.3233/BME-140984 IOS Press
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Swelling behavior and morphological properties of semi-IPN hydrogels based on ionic and non-ionic components Mehlika Pulat ∗ and Hediye ˙Irem Özgündüz Gazi Universitesi, Fen Fakültesi, Kimya Bölümü, Ankara, Turkey Received 14 September 2011 Accepted 9 January 2014 Abstract. Semi-interpenetrating polymer network (IPN) hydrogels with different compositions of poly(vinyl alcohol) (PVA), poly(acrylic acid) (PAA) and poly(acrylamide) (PAAm) were synthesized via free radical polymerization using ethylene glycol dimethacrylate (EGDMA) as crosslinker. The variations of swelling percentages (S%) with time, temperature and pH were determined for all hydrogels. Average S% values at pH = 7.4 and 37◦ C were determined to be 1660% for PAA/PVA, the most swollen hydrogel, and 550% for PAAm/PVA, the least swollen IPN-hydrogel. Swelling behaviors based on ionic and non-ionic components were also explained with detailed SEM micrographs of the hydrogels. Keywords: Hydrogels, acrylic acid, acryl amide, poly(vinyl alcohol), swelling percentage
1. Introduction Hydrogels are hydrophilic natured three-dimensional networks, held together by cross-linked chemical or physical bonds [1]. Hydrogels have been extensively studied and used for a large number of applications in the medical field such as controlled drug release matrices [2,3], enzyme and yeast cell immobilization [4], blood-contacting applications and others [5]. Interpenetrating polymer networks (IPNs) are mixtures of two cross-linked polymers. If one polymer is cross linked and the other is linear, the structure is called semi-IPN [6]. IPNs are preferred in a number of biotechnological and biomedical applications because of their certain unique biophysical properties such as ease of fabrication to various geometrical forms; soft and rubbery texture; minimum mechanical irritation to surrounding tissues; unusual stability to biofluids, etc. [7]. IPN structures are also used for the control of overall hydrogel hydrophilicity and drug release kinetic [8]. A wide range of so-called semi-IPN has been prepared dissolving a performed linear polymer in a hydrophilic monomer and crosslinking agent mixture which is subsequently polymerized. In this way a synthetic hydrogel network is formed around a primary polymer chain which is modifying the behavior of the hydrogel [9]. A wide *
Address for correspondence: Mehlika Pulat, Gazi Universitesi, Fen Fakültesi, Kimya Bölümü, Teknikokullar, Ankara, Turkey. E-mail: [email protected]. 0959-2989/14/$27.50 © 2014 – IOS Press and the authors. All rights reserved
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M. Pulat and H.I˙ Özgündüz / Swelling behavior and morphological properties of semi-IPN hydrogels
variety of linear polymers (e.g. polymethacrylates, polyurethanes and modified celluloses) have been used as interpenetrants in semi-IPNs hydrogels. The use of semi-IPNs in pH-sensitive or temperaturesensitive drug delivery systems has been well documented [10,11]. Polyelectrolyte gels are formed from cross-linking flexible polymer chains to which ionizable groups are attached [12]. These ionizable groups will completely or partially dissociate in solution to form strong or weak electrolyte groups along its chains. These charged groups produce an electrostatic repulsion force among themselves, which will enhance the expansion of the gel network [13,14]. In an anionic polymeric network containing carboxylic acid groups, ionization takes place as the pH of the external swelling medium increases above the pK of the ionizable moiety. The polymeric network becomes more hydrophilic as the degree of ionization increases [15,16]. Poly(vinyl alcohol) (PVA) is used as a basic material for a variety of biomedical applications including contact lenses materials, skin replacement material, reconstruction of vocal cords, artificial cartilage replacement, etc. because of their inherent nontoxicity, non-carcinogenicity, good biocompatibility and desirable physical properties such as elastic nature, high degree of swelling in aqueous solutions and good film forming property [17]. IPNs containing PVA have also gained wide pharmaceutical applications as drug delivery matrices or in the form of powders added to mixture of other excipient for tablet formation. Because of easy polymerization and biocompatible properties, acryl amide (AAm) and acrylic acid (AA) monomers are widely used to prepare the hydrogels [16]. In this study, we chose PAAm and PAA due to their hydrophilic natures, high water uptake capabilities and ease of processing. Moreover PAAm and PAA were preferred for their non-ionic and ionic properties, respectively. Incorporation of PVA into a PAA and PAAm network can be performed by using various methods, such as blending, grafting or forming IPNs [18]. Besides many studies about PAAm and PAA hydrogels, some investigations have also focused on their copolymeric hydrogels. The various copolymeric conformations could be used to arrange the swelling response of the hydrogels [19]. The aim of this presented study is to prepare a series of semi-IPN type hydrogel via free radical polymerization by using (NH4 )2 S2 O8 /Na2 S2 O5 redox pair and investigate the effects of the polymer composition on the swelling behaviors and morphological structure of the hydrogels. For this purpose PAA is used as ionic component while PAAm and PVA are chosen as non-ionic components. SEM analysis was also carried out to characterize the bulk structure and morphologies of hydrogels.
2. Materials and methods 2.1. Preparation of hydrogels In this study, a series of semi-IPN hydrogels based on PVA (Aldrich, degree of deacetylation is 75%), AA (Aldrich) and AAm (Aldrich) were prepared by radical polymerization procedure [16]. The reactions were started by a fix amout of (NH4 )2 S2 O8 /Na2 S2 O5 (Merck) redox pair at room temperature. The semiIPN structures were composed by using ethylene glycol dimethacrylate (EGDMA, Aldrich) as crosslinking agent. Detailed procedure is given below: 0.3 g/5 ml PVA-distilled water solution was prepared and mixed with the aqueous solutions of AA or AAm into a beaker. Total volume of the mixture was 7.5 ml. The amounts of AA and AAm were given in Table 1. The constant amount (0.1 ml) of EGDMA was added into beaker as crosslinker. After
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Table 1 Amount of AAm, AA and PVA in monomer mixture solutions used to form the hydrogels and gel formation percentages Hydrogel
AAm (mol/l) – 3 3 5
PAA/PVA P(AA-co-AAm)/PVA P(AA-co-AAm) PAAm/PVA
AA (mol/l) 5 3 3 –
PVA (g) 0.3 0.3 – 0.3
Gel formation (%) 98.0 89.3 96.2 81.1
0.05/0.05 g/g of (NH4 )2 S2 O8 /Na2 S2 O5 was interfused as initiator into this mixture, it was transferred from beaker to glass tubes. The polymerization was carried out for 24 h at room temperature. At the end of this period, glass tubes were carefully broken and obtained hydrogel rod were cut into small discs of 0.5 cm length. The gel discs were washed several times with distilled water to remove unreacted chemicals, dried first in air and then in a vacuum oven at 37.0◦ C [16,20–23]. The average thicknesses of dried hydrogels measured with a micrometer were found in the range of 0.30–0.40 cm according to the content of the gel matrix. 2.2. Determination of the gel formation percentages The gel formation percentages of the samples were gravimetrically determined as follows [23,24]: The dried hydrogel were weighed and then placed in distilled water to extract the unreacted monomers. Extraction medium was refreshed several times during 48 h and then the hydrogels were then taken from the medium, dried in a vacuum oven at 40◦ C to constant weight. The gel formations (%) were determined using: Gel formation (%) =
m × 100, m0
(1)
where m is the weight of the dried hydrogel after extraction and m0 is the weight of the dried hydrogel before extraction. All measurements were performed in triplicate. 2.3. Swelling tests Swelling tests of hydrogel samples were gravimetrically carried out in three steps. In the first step, dried hydrogel pieces were left to swell in Britton–Robinson tampon (BRT) (Riedel–de Haën) solution (pH = 7.4) at 37◦ C. Swollen gels removed from the swelling medium at regular intervals were dried superficially with filter paper, weighed, and placed into the same bath. The measurements were performed until a constant weight was reached for each sample. The percentage swelling (S%) values were calculated from the following equation [22,25,26]: S% =
mw − md × 100, md
(2)
where mw is the wet weight of the sample and md is the dry weight of the sample before swelling. The incubation times for all gels were approximately 24 h. In the second step, the dried hydrogel pieces were swollen in BRT (pH = 7.4) solutions at different temperatures ranging from 4.0 to 60.0◦ C to investigate the effect of temperature on swelling behaviors.
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At the end of 24 h, the swollen gels were removed from the swelling medium, dried superficially with filter paper, and weighed. S% values were calculated using Eq. (2). In the last step, the dried hydrogel pieces were swollen in different BRT solutions at various pH values between 2 and 12 to investigate the effect of pH on the swelling behaviors. Temperature and swelling time were kept constant (37◦ C and 24 h, respectively). The swollen gels were removed from the swelling medium, dried superficially with filter paper, and weighed. S% values were calculated using Eq. (2). The reproducible results for all swelling studies are obtained with triplicate measurements. 2.4. SEM observation PAA, PAAm, PAA/PVA, PAAm/PVA, P(AA-co-AAm)/PVA and P(AA-co-AAm) hydrogel samples swollen to equilibrium in water at room temperature were removed and placed in a deep freezer at −20◦ C for 24 h and then transferred into a freeze dryer (Christ-Alfa 2–4 Model, Martin Christ GmbH, Germany) at −85◦ C for 1 week. The dried and swollen straps were coated with 200 Å Au. The surface micrographs of the samples were obtained with a scanning electron microscope (JEOL, JSM 6060A, Japan). 3. Results and discussion 3.1. Composition of the hydrogels General mechanisms about the formation of semi-IPNs are well documented in the literature [27– 30]. Similar mechanisms could be suggested for the IPNs produced in this study. Persulfate initiator is reduced to (SO4 )−· anion-radical. This radical abstracts hydrogen from monomer to form vinyl radicals. Thus, the radically initiated polymerization reactions of AA or AAm monomers were performed [23, 30]. It can be thought that PAA or PAAm are the host polymer in this semi-IPN system. While EGDMA provide the cross-linking of vinyl polymer chains (PAA or PAAm), PVA contribute into the structure as guest polymer. The gel formation percentage values of the hydrogels calculated gravimetrically are presented in Table 1. In general, high gel formation values were mostly obtained so this procedure is convenient for preparing the semi-IPN type hydrogels with PVA and vinylic polymers. The highest and the lowest gel formation percentages were obtained for PAA/PVA and PAAm/PVA semi-IPN type hydrogels respectively. IPN formation between PAA and PVA chains could also be simplified by the anionic structure of PAA, thus gel formation of PAA/PVA hydrogels would be favorable than PAAm/PVA pairs. It is concluded that adding of PVA as guest component into the structure, gel formation yields slightly decreased. However, from the date given in the table, the gel formation percentages were evaluated as satisfactory by comparison with the literature values. 3.2. Swelling behaviors of hydrogels Figure 1 represents the variation of S% values with time at pH = 7.4, 37◦ C. Four different hydrogels are prepared in this study. Swelling values of pure PAAm and PAA hydrogels based on our previous studies are also added into the same graphic for explanation and comparison of the swelling behaviors [23]. It is seen that the S% values increases with time at first and then keep constant near 24 h. According to the ionic character the most swollen gel is PAA. PAA/PVA presents lower S% value than pure PAA
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Fig. 1. Variation of S% values with time at 37.0◦ C, pH = 7.4. (The values belong to pure PAA and PAAm hydrogels are based on our previous study, Ref. [23].)
Fig. 2. The variation of S% values with temperature at pH = 7.4 for 24 h.
hydrogel because of the non-ionic structure of PVA. The least swollen gel is PAAm. As PVA has more hydrophilic character than PAAm, PAAm/PVA features higher S% value than pure PAAm hydrogel. While PVA is being as a guest polymer in P(AA-co-AAm), the swelling percentages was decreased from 1500% to 900%. This might be non-ionic structure of PVA. In general, hydrogels included PAA present more swellable character than the hydrogels based on PAAm. Figure 2 presents the variation of S% values of hydrogels with temperature at pH = 7.4 for 24 h. As seen from this figure, all hydrogels at high temperatures swell much more than the hydrogels at low temperatures. It is known that the swelling of hydrogels including PAA and PAAm are positively depends on the temperature. While temperature rises, thermal mobility of the polymer chains increase and H-bonds were broken thereby hydrogels can easily swell [31,32]. Low S% values were obtained for
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M. Pulat and H.I˙ Özgündüz / Swelling behavior and morphological properties of semi-IPN hydrogels
Fig. 3. The variation of S% values with pH at 37◦ C, 24 h.
all hydrogels at 4◦ C. PAAm/PVA hydrogel was not stable over 50◦ C. As swelling values of PAA/PVA and P(AA-co-AAm) hydrogels exhibit great differences between 4◦ C and 40◦ C, it is thought that these hydrogels are sensitive to variations in temperature at this range [24,33]. Figure 3 represents the variation of S% values with pH at 37◦ C, 24 h. PAAm/PVA hydrogel is not stable over pH = 8.0. Low swelling percentages are obtained for all hydrogels at pH = 2.0 relative to other pH values. Except PAAm/PVA, it is seen that the maximum extent of swelling were reached about pH = 7.4, this being due to the complete dissociation of acid groups of AA at this pH value. Dissociation constant of AA is pKa = 4.25 and the single-step swelling versus pH curves are observed [16,23]. As swelling values of PAA/PVA and P(AA-co-AAm) hydrogels exhibit great differences between pH values of 2.0–8.0, it is thought that these hydrogels are sensitive to the variations in pH at this range [22,34]. 3.3. SEM analysis SEM micrographs of dry and swollen hydrogels were presented in Fig. 4. Because all of the dry hydrogels have in similar views, just one micrograph was presented as dry surface sample. The morphological differences between dry and wet state of hydrogels can be clearly observed. The porosity values of hydrogels were directly determined from SEM micrographs and presented in Table 2 [35]. As seen from this table, P(AA-co-AAm) hydrogel has the most porous structure than others. The less swollen hydrogel, PAAm/PVA has just a few pores on the surface. The low swollen value of this hydrogel is explicable with either its non-ionic and porous structure. P(AA-co-AAm)/PVA hydrogel has large pores but its average pore density is little. The most swollen hydrogel, PAA/PVA has large pores and its pore density value is higher than PAAm/PVA and P(AA-co-AAm)/PVA hydrogels. 4. Conclusion Four different ionic and non-ionic IPN-hydrogels were prepared by using AAm, AA and PVA monomers via chemically inducing method. EGDMA is chosen as crosslinker. Gel formation capacities were studied and high gelation percentages were found for all hydrogels. The variations of swelling values (%) with time, temperature and pH were determined for all hydrogels. The ionizing capacity of
M. Pulat and H.I˙ Özgündüz / Swelling behavior and morphological properties of semi-IPN hydrogels
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Fig. 4. SEM micrographs of surfaces of (a) dry P(AA-co-AAm), (b) swollen PAA/PVA, (c) swollen P(AA-co-AAm), (d) swollen P(AA-co-AAm)/PVA and (e) PAAm/PVA swollen hydrogels.
the polymers directly affects the swelling capacities of the hydrogels. Generally, PAA included hydrogels swell much more then the hydrogels produced by using PAAm and PVA which are the non-ionic components of the structures. The detailed SEM micrographs present the morphologic differences between dry and swollen hydrogels.
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M. Pulat and H.I˙ Özgündüz / Swelling behavior and morphological properties of semi-IPN hydrogels Table 2 Pore characteristics of the hydrogels Hydrogel PAA/PVA P(AA-co-AAm) P(AA-co-AAm)/PVA PAAm/PVA
Average pore density (no. of pores/cm2 ) 8.6 × 104 32 × 104 4.2 × 104 0.8 × 104
Average pore radius (µm) 35 ± 1.2 2.2 ± 0.4 45 ± 2.5 8.3 ± 1.0
Acknowledgement The financial and technical support of the research from Gazi University Research Fund is gratefully acknowledged. References [1] C. Elvira, J.F. Mano, J.S. Roman and R.L. Reis, Starch-based biodegradable hydrogels with potential biomedical applications as drug delivery systems, Biomaterials 23(9) (2002), 1955. [2] O. Güven and M. Sen, ¸ Preparation and characterization of poly(n-vinyl 2-pyrrolidone) hydrogels, Polymer 32(13) (1991), 2491. [3] A.S. Hoffman, Hydrogels for biomedical applications, Advanced Drug Delivery Reviews 54(1) (2002), 3. [4] G. Aykut, V.H. Hasırcı and G. Alaeddino˘glu, Immobilization of yeast cells in acrylamide gel matrix, Biomaterials 9 (1998), 168. [5] M.D. Blanco, C. Gómez, O. García and J.M. Teijón, Ara-C release from poly(acrylamide-co-monomethyl itaconate) hydrogels: in vitro and in vivo studies, Polymer Gels and Networks 6(1) (1998), 57. [6] W. Wang and A. Wang, Synthesis and swelling properties of pH-sensitive semi-IPN superabsorbent hydrogels based on sodium alginate-g-poly(sodium acrylate) and polyvinylpyrrolidone, Carbohydrate Polymers 80 (2010), 1028. [7] I.M. El-Sherbiny, R.J. Lins, E.M. Abdel-Bary and D.R.K. Harding, Preparation, characterization, swelling and in vitro drug release behaviour of poly[N-acryloylglycine-chitosan] interpolymeric pH and thermally-responsive hydrogels, European Polymer Journal 41 (2005), 2584. [8] Y.H. Bae and S.W. Kim, Hydrogel delivery systems based on polymer blends, block copolymers, and interpenetrating networks, Advanced Drug Delivery Reviews 11 (1993), 109. [9] M. Pulat, H. Eksi and U. Abbasoglu, Fluconazole release from hydrogels including acrylamide-acrylic acid-itaconic acid, and their microbiological interactions, Journal of Biomaterials Science – Polymer Edition 19(2) (2008), 193. [10] D. Schmaljohann, Thermo- and pH-responsive polymers in drug delivery, Advanced Drug Delivery Reviews 58 (2006), 1655. [11] K.D. Yao, T. Peng, M.X. Xu, C. Yuan, M.F.A. Goosen and Q.Q. Zhang, pH-dependent hydrolysis and drug-release of chitosan polyether interpenetrating polymer network hydrogel, Polymer International 34(2) (1994), 213. [12] E. Rodriguez and I. Katime, Behavior of acrylic acid–itaconic acid hydrogels in swelling, shrinking, and uptakes of some metal ions from aqueous solution, Journal of Applied Polymer Science 90 (2003), 530. [13] Y. Chu, M. McGlade, P.P. Varanasi and S. Varanasi, pH induced swelling kinetics of polyelectrolyte hydrogels, Journal of Applied Polymer Science 58 (1995), 2161. [14] N.B. Milosavljevic, N.Z. Milasinovic, I.G. Popovic, J.M. Filipovic and M.T.K. Krusic, Preparation and characterization of pH-sensitive hydrogels based on chitosan, itaconic acid and methacrylic acid, Polymer International 60(3) (2011), 443. [15] A.R. Khare and N.A. Peppas, Swelling deswelling of anionic copolymer gels, Biomaterials 6(7) (1995), 559. [16] M. Pulat and H. Ek¸si, Determination of swelling behavior and morphological properties of poly(acrylamide-co-itaconic acid) and poly(acrylic acid-co-itaconic acid) copolymeric hydrogels, Journal of Applied Polymer Science 102(6) (2006), 5994. [17] A.K. Bajpai, J. Bajpai and S. Shukla, Water sorption through a semi-interpenetrating polymer network (IPN) with hydrophilic and hydrophobic chains, Reactive & Functional Polymers 50 (2001), 9. [18] S.H. Bodugoz, C.E. Macias, J.H. Kung and O.K. Muratoglu, Poly(vinyl alcohol)–acrylamide hydrogels as load-bearing cartilage substitute, Biomaterials 30 (2009), 589. [19] M. Pulat and D. Asıl, Fluconazole release through semi-interpenetrating polymer network hydrogels based on chitosan, acrylic acid and citraconic acid, Journal of Applied Polymer Science 113 (2009), 2613.
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[20] R. Hernandez, E. Perez, C. Mijangos and D. Lopez, Poly(vinyl alcohol)–poly(acrylic acid) interpenetrating networks, Study on phase separation and molecular motions, Polymer 46 (2005), 7066. [21] M. Pulat, N. Tan and F.K. Onurdag, Swelling dynamics of IPN hydrogels including acrylamide–acrylic acid–chitosan and evaluation of their potential for controlled release of piperacillin–tazobactam, Journal of Applied Polymer Science 120(1) (2011), 441. [22] M.D. Blanco, M.V. Bernardo, C. Teijon, R.L. Sastre and J.M. Teijon, Transdermal application of bupivacaine-loaded poly (acrylamide(a)-co-monomethylitaconate) hydrogels, International Journal of Pharmaceutics 255(1) (2003), 99. [23] M. Pulat and M. Çetin, Pantoprazole-Na release from poly(acrylamide-co-crotonic acid) and poly(acrylic acid-co-crotonic acid) hydrogels, Journal of Bioactive and Compatible Polymers 23 (2008), 305. [24] K.S. Chen, Y.A. Ku, H.R. Lin, T.R. Yan, D.C. Sheu, T.M. Chen and F.H. Lin, Preparation and characterization of pH sensitive poly(n-vinyl-2-pyrrolidone/itaconic acid) copolymer hydrogels, Materials Chemistry and Physics 91(2,3) (2005), 484. [25] M. Pulat, E. Memi¸s and M. Gümü¸sderelio˘glu, Adsorption of bovine serum albumin onto surface-modified polyhydroxyethyl methacrylate beads, Journal of Biomaterials Applications 17(3) (2003), 237. [26] G.H. Hsiue, J.A. Guu and C.C. Cheng, Poly(2-hydroxyethyl methacrylate) film as a drug delivery system for piocarpine, Biomaterials 22 (2001), 1763. [27] G.R. Mahdavinia, A. Pourjavadi, H. Hosseinzadeh and M.J. Zohuriaan, Modified chitosan. 4. Superabsorbent hydrogels from poly(acrylamide-co-acrylic acid) grafted chitosan with salt- and pH-responsiveness properties, Eurpean Polymer Journal 40(7) (2004), 1399. [28] T.W.G. Solomons, Organic Chemistry, Wiley, New York, 1996. [29] M.N.V. Ravikumar, A review of chitin and chitosan applications, Reactive Functional Polymers 46 (2000), 1. [30] L. Yin, L. Fei, F. Cui, C. Tang and C. Yin, Superporous hydrogels containing poly(acrylic acid-co-acrylamide)/ O-carboxymethyl chitosan interpenetrating polymer networks, Biomaterials 28 (2007), 1258. [31] H. Katona, K. Maruyama, K. Sanui, T. Okano and Y. Sakuai, Thermoresponsive swelling and drug release switching of interpenetrating polymer networks composed of poly (acrylamide-co-butyl methacrylate) and poly (acrylic-acid), Journal of Controlled Release 16 (1991), 215. [32] X.C. Xiao, L.Y. Chu, W.M. Chen and J.H. Zhu, Monodispersed thermoresponsive hydrogel microspheres with a volume phase transition driven by hydrogen bonding, Polymer 46 (2005), 3199. [33] B. Ta¸sdelen, N. Kayaman, O. Güven and B.M. Baysal, Preparation of poly(n-isopropylacrylamide/itaconic acid) copolymeric hydrogels and their drug release behavior, International Journal of Pharmaceutics 278 (2004), 343. [34] M. Sen ¸ and O. Güven, Dynamic deswelling studies of poly(n-vinyl-2-pyrrolidone/itaconic acid) hydrogels swollen in water and terbinafine hydrochloride solutions, European Polymer Journal 38(4) (2002), 751. [35] M. Pulat and C. Senvar, ¸ Structural and surface-properties of polyurethane membranes of different porosities, Polymer Testing 14(2) (2002), 115.
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Swelling behavior and morphological properties of semi-IPN hydrogels based on ionic and non-ionic components Mehlika Pulat ∗ and Hediye ˙Irem Özgündüz Gazi Universitesi, Fen Fakültesi, Kimya Bölümü, Ankara, Turkey Received 14 September 2011 Accepted 9 January 2014 Abstract. Semi-interpenetrating polymer network (IPN) hydrogels with different compositions of poly(vinyl alcohol) (PVA), poly(acrylic acid) (PAA) and poly(acrylamide) (PAAm) were synthesized via free radical polymerization using ethylene glycol dimethacrylate (EGDMA) as crosslinker. The variations of swelling percentages (S%) with time, temperature and pH were determined for all hydrogels. Average S% values at pH = 7.4 and 37◦ C were determined to be 1660% for PAA/PVA, the most swollen hydrogel, and 550% for PAAm/PVA, the least swollen IPN-hydrogel. Swelling behaviors based on ionic and non-ionic components were also explained with detailed SEM micrographs of the hydrogels. Keywords: Hydrogels, acrylic acid, acryl amide, poly(vinyl alcohol), swelling percentage
1. Introduction Hydrogels are hydrophilic natured three-dimensional networks, held together by cross-linked chemical or physical bonds [1]. Hydrogels have been extensively studied and used for a large number of applications in the medical field such as controlled drug release matrices [2,3], enzyme and yeast cell immobilization [4], blood-contacting applications and others [5]. Interpenetrating polymer networks (IPNs) are mixtures of two cross-linked polymers. If one polymer is cross linked and the other is linear, the structure is called semi-IPN [6]. IPNs are preferred in a number of biotechnological and biomedical applications because of their certain unique biophysical properties such as ease of fabrication to various geometrical forms; soft and rubbery texture; minimum mechanical irritation to surrounding tissues; unusual stability to biofluids, etc. [7]. IPN structures are also used for the control of overall hydrogel hydrophilicity and drug release kinetic [8]. A wide range of so-called semi-IPN has been prepared dissolving a performed linear polymer in a hydrophilic monomer and crosslinking agent mixture which is subsequently polymerized. In this way a synthetic hydrogel network is formed around a primary polymer chain which is modifying the behavior of the hydrogel [9]. A wide *
Address for correspondence: Mehlika Pulat, Gazi Universitesi, Fen Fakültesi, Kimya Bölümü, Teknikokullar, Ankara, Turkey. E-mail: [email protected]. 0959-2989/14/$27.50 © 2014 – IOS Press and the authors. All rights reserved
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M. Pulat and H.I˙ Özgündüz / Swelling behavior and morphological properties of semi-IPN hydrogels
variety of linear polymers (e.g. polymethacrylates, polyurethanes and modified celluloses) have been used as interpenetrants in semi-IPNs hydrogels. The use of semi-IPNs in pH-sensitive or temperaturesensitive drug delivery systems has been well documented [10,11]. Polyelectrolyte gels are formed from cross-linking flexible polymer chains to which ionizable groups are attached [12]. These ionizable groups will completely or partially dissociate in solution to form strong or weak electrolyte groups along its chains. These charged groups produce an electrostatic repulsion force among themselves, which will enhance the expansion of the gel network [13,14]. In an anionic polymeric network containing carboxylic acid groups, ionization takes place as the pH of the external swelling medium increases above the pK of the ionizable moiety. The polymeric network becomes more hydrophilic as the degree of ionization increases [15,16]. Poly(vinyl alcohol) (PVA) is used as a basic material for a variety of biomedical applications including contact lenses materials, skin replacement material, reconstruction of vocal cords, artificial cartilage replacement, etc. because of their inherent nontoxicity, non-carcinogenicity, good biocompatibility and desirable physical properties such as elastic nature, high degree of swelling in aqueous solutions and good film forming property [17]. IPNs containing PVA have also gained wide pharmaceutical applications as drug delivery matrices or in the form of powders added to mixture of other excipient for tablet formation. Because of easy polymerization and biocompatible properties, acryl amide (AAm) and acrylic acid (AA) monomers are widely used to prepare the hydrogels [16]. In this study, we chose PAAm and PAA due to their hydrophilic natures, high water uptake capabilities and ease of processing. Moreover PAAm and PAA were preferred for their non-ionic and ionic properties, respectively. Incorporation of PVA into a PAA and PAAm network can be performed by using various methods, such as blending, grafting or forming IPNs [18]. Besides many studies about PAAm and PAA hydrogels, some investigations have also focused on their copolymeric hydrogels. The various copolymeric conformations could be used to arrange the swelling response of the hydrogels [19]. The aim of this presented study is to prepare a series of semi-IPN type hydrogel via free radical polymerization by using (NH4 )2 S2 O8 /Na2 S2 O5 redox pair and investigate the effects of the polymer composition on the swelling behaviors and morphological structure of the hydrogels. For this purpose PAA is used as ionic component while PAAm and PVA are chosen as non-ionic components. SEM analysis was also carried out to characterize the bulk structure and morphologies of hydrogels.
2. Materials and methods 2.1. Preparation of hydrogels In this study, a series of semi-IPN hydrogels based on PVA (Aldrich, degree of deacetylation is 75%), AA (Aldrich) and AAm (Aldrich) were prepared by radical polymerization procedure [16]. The reactions were started by a fix amout of (NH4 )2 S2 O8 /Na2 S2 O5 (Merck) redox pair at room temperature. The semiIPN structures were composed by using ethylene glycol dimethacrylate (EGDMA, Aldrich) as crosslinking agent. Detailed procedure is given below: 0.3 g/5 ml PVA-distilled water solution was prepared and mixed with the aqueous solutions of AA or AAm into a beaker. Total volume of the mixture was 7.5 ml. The amounts of AA and AAm were given in Table 1. The constant amount (0.1 ml) of EGDMA was added into beaker as crosslinker. After
M. Pulat and H.I˙ Özgündüz / Swelling behavior and morphological properties of semi-IPN hydrogels
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Table 1 Amount of AAm, AA and PVA in monomer mixture solutions used to form the hydrogels and gel formation percentages Hydrogel
AAm (mol/l) – 3 3 5
PAA/PVA P(AA-co-AAm)/PVA P(AA-co-AAm) PAAm/PVA
AA (mol/l) 5 3 3 –
PVA (g) 0.3 0.3 – 0.3
Gel formation (%) 98.0 89.3 96.2 81.1
0.05/0.05 g/g of (NH4 )2 S2 O8 /Na2 S2 O5 was interfused as initiator into this mixture, it was transferred from beaker to glass tubes. The polymerization was carried out for 24 h at room temperature. At the end of this period, glass tubes were carefully broken and obtained hydrogel rod were cut into small discs of 0.5 cm length. The gel discs were washed several times with distilled water to remove unreacted chemicals, dried first in air and then in a vacuum oven at 37.0◦ C [16,20–23]. The average thicknesses of dried hydrogels measured with a micrometer were found in the range of 0.30–0.40 cm according to the content of the gel matrix. 2.2. Determination of the gel formation percentages The gel formation percentages of the samples were gravimetrically determined as follows [23,24]: The dried hydrogel were weighed and then placed in distilled water to extract the unreacted monomers. Extraction medium was refreshed several times during 48 h and then the hydrogels were then taken from the medium, dried in a vacuum oven at 40◦ C to constant weight. The gel formations (%) were determined using: Gel formation (%) =
m × 100, m0
(1)
where m is the weight of the dried hydrogel after extraction and m0 is the weight of the dried hydrogel before extraction. All measurements were performed in triplicate. 2.3. Swelling tests Swelling tests of hydrogel samples were gravimetrically carried out in three steps. In the first step, dried hydrogel pieces were left to swell in Britton–Robinson tampon (BRT) (Riedel–de Haën) solution (pH = 7.4) at 37◦ C. Swollen gels removed from the swelling medium at regular intervals were dried superficially with filter paper, weighed, and placed into the same bath. The measurements were performed until a constant weight was reached for each sample. The percentage swelling (S%) values were calculated from the following equation [22,25,26]: S% =
mw − md × 100, md
(2)
where mw is the wet weight of the sample and md is the dry weight of the sample before swelling. The incubation times for all gels were approximately 24 h. In the second step, the dried hydrogel pieces were swollen in BRT (pH = 7.4) solutions at different temperatures ranging from 4.0 to 60.0◦ C to investigate the effect of temperature on swelling behaviors.
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At the end of 24 h, the swollen gels were removed from the swelling medium, dried superficially with filter paper, and weighed. S% values were calculated using Eq. (2). In the last step, the dried hydrogel pieces were swollen in different BRT solutions at various pH values between 2 and 12 to investigate the effect of pH on the swelling behaviors. Temperature and swelling time were kept constant (37◦ C and 24 h, respectively). The swollen gels were removed from the swelling medium, dried superficially with filter paper, and weighed. S% values were calculated using Eq. (2). The reproducible results for all swelling studies are obtained with triplicate measurements. 2.4. SEM observation PAA, PAAm, PAA/PVA, PAAm/PVA, P(AA-co-AAm)/PVA and P(AA-co-AAm) hydrogel samples swollen to equilibrium in water at room temperature were removed and placed in a deep freezer at −20◦ C for 24 h and then transferred into a freeze dryer (Christ-Alfa 2–4 Model, Martin Christ GmbH, Germany) at −85◦ C for 1 week. The dried and swollen straps were coated with 200 Å Au. The surface micrographs of the samples were obtained with a scanning electron microscope (JEOL, JSM 6060A, Japan). 3. Results and discussion 3.1. Composition of the hydrogels General mechanisms about the formation of semi-IPNs are well documented in the literature [27– 30]. Similar mechanisms could be suggested for the IPNs produced in this study. Persulfate initiator is reduced to (SO4 )−· anion-radical. This radical abstracts hydrogen from monomer to form vinyl radicals. Thus, the radically initiated polymerization reactions of AA or AAm monomers were performed [23, 30]. It can be thought that PAA or PAAm are the host polymer in this semi-IPN system. While EGDMA provide the cross-linking of vinyl polymer chains (PAA or PAAm), PVA contribute into the structure as guest polymer. The gel formation percentage values of the hydrogels calculated gravimetrically are presented in Table 1. In general, high gel formation values were mostly obtained so this procedure is convenient for preparing the semi-IPN type hydrogels with PVA and vinylic polymers. The highest and the lowest gel formation percentages were obtained for PAA/PVA and PAAm/PVA semi-IPN type hydrogels respectively. IPN formation between PAA and PVA chains could also be simplified by the anionic structure of PAA, thus gel formation of PAA/PVA hydrogels would be favorable than PAAm/PVA pairs. It is concluded that adding of PVA as guest component into the structure, gel formation yields slightly decreased. However, from the date given in the table, the gel formation percentages were evaluated as satisfactory by comparison with the literature values. 3.2. Swelling behaviors of hydrogels Figure 1 represents the variation of S% values with time at pH = 7.4, 37◦ C. Four different hydrogels are prepared in this study. Swelling values of pure PAAm and PAA hydrogels based on our previous studies are also added into the same graphic for explanation and comparison of the swelling behaviors [23]. It is seen that the S% values increases with time at first and then keep constant near 24 h. According to the ionic character the most swollen gel is PAA. PAA/PVA presents lower S% value than pure PAA
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Fig. 1. Variation of S% values with time at 37.0◦ C, pH = 7.4. (The values belong to pure PAA and PAAm hydrogels are based on our previous study, Ref. [23].)
Fig. 2. The variation of S% values with temperature at pH = 7.4 for 24 h.
hydrogel because of the non-ionic structure of PVA. The least swollen gel is PAAm. As PVA has more hydrophilic character than PAAm, PAAm/PVA features higher S% value than pure PAAm hydrogel. While PVA is being as a guest polymer in P(AA-co-AAm), the swelling percentages was decreased from 1500% to 900%. This might be non-ionic structure of PVA. In general, hydrogels included PAA present more swellable character than the hydrogels based on PAAm. Figure 2 presents the variation of S% values of hydrogels with temperature at pH = 7.4 for 24 h. As seen from this figure, all hydrogels at high temperatures swell much more than the hydrogels at low temperatures. It is known that the swelling of hydrogels including PAA and PAAm are positively depends on the temperature. While temperature rises, thermal mobility of the polymer chains increase and H-bonds were broken thereby hydrogels can easily swell [31,32]. Low S% values were obtained for
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Fig. 3. The variation of S% values with pH at 37◦ C, 24 h.
all hydrogels at 4◦ C. PAAm/PVA hydrogel was not stable over 50◦ C. As swelling values of PAA/PVA and P(AA-co-AAm) hydrogels exhibit great differences between 4◦ C and 40◦ C, it is thought that these hydrogels are sensitive to variations in temperature at this range [24,33]. Figure 3 represents the variation of S% values with pH at 37◦ C, 24 h. PAAm/PVA hydrogel is not stable over pH = 8.0. Low swelling percentages are obtained for all hydrogels at pH = 2.0 relative to other pH values. Except PAAm/PVA, it is seen that the maximum extent of swelling were reached about pH = 7.4, this being due to the complete dissociation of acid groups of AA at this pH value. Dissociation constant of AA is pKa = 4.25 and the single-step swelling versus pH curves are observed [16,23]. As swelling values of PAA/PVA and P(AA-co-AAm) hydrogels exhibit great differences between pH values of 2.0–8.0, it is thought that these hydrogels are sensitive to the variations in pH at this range [22,34]. 3.3. SEM analysis SEM micrographs of dry and swollen hydrogels were presented in Fig. 4. Because all of the dry hydrogels have in similar views, just one micrograph was presented as dry surface sample. The morphological differences between dry and wet state of hydrogels can be clearly observed. The porosity values of hydrogels were directly determined from SEM micrographs and presented in Table 2 [35]. As seen from this table, P(AA-co-AAm) hydrogel has the most porous structure than others. The less swollen hydrogel, PAAm/PVA has just a few pores on the surface. The low swollen value of this hydrogel is explicable with either its non-ionic and porous structure. P(AA-co-AAm)/PVA hydrogel has large pores but its average pore density is little. The most swollen hydrogel, PAA/PVA has large pores and its pore density value is higher than PAAm/PVA and P(AA-co-AAm)/PVA hydrogels. 4. Conclusion Four different ionic and non-ionic IPN-hydrogels were prepared by using AAm, AA and PVA monomers via chemically inducing method. EGDMA is chosen as crosslinker. Gel formation capacities were studied and high gelation percentages were found for all hydrogels. The variations of swelling values (%) with time, temperature and pH were determined for all hydrogels. The ionizing capacity of
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Fig. 4. SEM micrographs of surfaces of (a) dry P(AA-co-AAm), (b) swollen PAA/PVA, (c) swollen P(AA-co-AAm), (d) swollen P(AA-co-AAm)/PVA and (e) PAAm/PVA swollen hydrogels.
the polymers directly affects the swelling capacities of the hydrogels. Generally, PAA included hydrogels swell much more then the hydrogels produced by using PAAm and PVA which are the non-ionic components of the structures. The detailed SEM micrographs present the morphologic differences between dry and swollen hydrogels.
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M. Pulat and H.I˙ Özgündüz / Swelling behavior and morphological properties of semi-IPN hydrogels Table 2 Pore characteristics of the hydrogels Hydrogel PAA/PVA P(AA-co-AAm) P(AA-co-AAm)/PVA PAAm/PVA
Average pore density (no. of pores/cm2 ) 8.6 × 104 32 × 104 4.2 × 104 0.8 × 104
Average pore radius (µm) 35 ± 1.2 2.2 ± 0.4 45 ± 2.5 8.3 ± 1.0
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