Katarzyna BIALIK-WĄS, Bożena TYLISZCZAK, Edyta WILK, Krzysztof PIELICHOWSKI ? Department of Chemistry and Technology of Polymers, Faculty of Chemical Engineering and Technology, Cracow University of Technology, Cracow, Poland
This paper describes new method of preparation of poly(acrylic acid) ? based hydrogel materials under microwave irradiation. The application of poly(ethylene glycol) (PEG), biodegradable and non-toxic polymer, which is widely used in medicine and pharmacy, enabled to control the degree of swelling and degradation of poly(acrylic) matrix. The obtained acrylic hydrogels modified by PEG were investigated towards: swelling ability in distilled water, 0.9% of NaCl solution and 0.9% of MgCl2 solution, degradation in simulated body fluids (SBF and Ringer?s solution) and the thermal stability by thermo-gravimetric analysis (TGA).
Please cite as: CHEMIK 2013, 67, 2, 99-104
Nowadays polymers are widely applied as biomedical materials, because they have the following characteristics: biocompatibility, biophosphates, bioactivity, non-toxicity, chemical resistance. Among them important groups represent the hydrogels, whose dynamic development began in 1960. The great turning point was the discovery of Wichterle and Lim (1960), who studied poly(2-hydroxyl-ethyl-methacrylate) (PHEMA) hydrogels for production of soft contact lenses. Since then the search for new applications of hydrogels started and clarified the terminology proposed [1÷3] . Hydrogels are defined as smart, active, intelligent, programmed and with shape memory polymeric materials. They constitute an appropriate biomaterial in implantology (for example for the corneal implants), tissue engineering, hydrogel wound dressings and hybrid organs [4, 5].
From the point of medicine an interesting application of hydrogels are interactive wound dressings, which belong to the most modern third-generation of dressing materials. They are applied in the treatment wounds with slow ? healing (decubitus ulcers, venous ulcers, diabetic foot ulcers), which are in the phase of granulation and epithelization and also in case of second-degree burns and post-operative wounds, for covering donor sections in the skin transplantation practice [6÷9]. The new-generation dressings fulfill the most important requirements and ensure an optimal environment for the natural processes taking place in the healing of the wound through a proper thermoregulation and moisture, gaseous exchange and pH (slightly acidic pH, bacteriostatic activity). Furthermore, they cleanse wounds of the necrotic tissue through appropriate irrigation, they prevent the creation of scabs and fibrins, which accelerates epithelization and limits the development of the infection and the dispersion of the bacteria, while the replacement of the dressing is easy and painless [10÷12]. This article presents the investigations results concerning preparation of hydrogels based on poly(acrylic acid) modified PEG, using microwave irradiation.
In the conducted investigations the following analytically quality chemicals were used: acrylic acid (AA), potassium hydroxide (KOH), ammonium persulfate (APS), N, N?-methylen(bisacrylamide) (NMBA) and poly(ethylene glycol) (PEG) 6000. All used reagents were from company POCh Gliwice (Poland).
Synthesis of PAA/PEG hydrogel was conducted in the following order: the appropriate amount of acrylic acid (45 ml) was mixed with 40% KOH solution (50 ml). This procedure was carried out in a cooling medium (cold water), because the reaction is highly exothermic. After reaching the ambient temperature (20°C), poly(ethylene glycol) (5%, 10%, 15% wt), initiator (1ml) and cross-linking agent (NMBA) (1.5 ml, 2 ml, 2.5 ml), were added. The synthesis of hydrogels was carried out under microwave irradiation (300 W, 3 min.) [13÷15]. The composition PAA/PEG is showed in Table 1.
2.3. The swelling behaviour evaluation
All of the obtained hydrogels PAA/PEG which contained a different amount of cross-linking agent and poly(ethylene glycol) in polymeric composition, were tested for use in medicine and pharmacy. The ability of swelling was studied in distilled water, 0.9% NaCl solution and 0.9% MgCl2 solution. The dried sample of hydrogel, which weighed about 1g, was immersed in 300 ml of the prepared solution for 1 h. After this time the swollen hydrogel was weighed. The investigations were carried out at room temperature (20°C) and under atmospheric pressure with using the static and dynamic method. The difference lies in the application of a magnetic stirrer in the second case. The hydrogel, which was placed in water, performed rotational movements under the influence of the mixing. That is why, the interaction with fluids molecules was easier. The degree of swelling was calculated according to the following formula:
Where: W1 and W0 refer to the weight of the hydrogel in swollen and dried state respectively. The swelling behavior of hydrogel depends on type of polymer (composition) and properties of the absorbed medium.
2.4. Degradation in simulated body fluids
The tendency to degradation of obtained hydrogels was studied in simulated body fluids: SBF (pH = 7.4), Ringer?s solution (pH = 6.66) and in distilled water (pH = 6.57). 1 g samples were placed in solutions for a period of 42 days. During these experiments, values of pH were determined every seven days.
2.5. Thermal analysis (TGA)
Based on the thermo-gravimetric data (TG) the impact of poly(ethylene glycol) on the thermal stability of PAA/PEG hydrogels, was analyzed. The thermo-gravimetric analyzer TG 209 of Netzsch was applied. Measurements were conducted in air atmosphere and the samples were heated from 25°C to 200°C at 10°C /min.
3. Results and discussion
3.1. evaluation of the swelling behavior
The swelling behavior of hydrogels in distilled water (Figs. 1 and 2) in 0.9% NaCl solution (Figs. 3 and 4) and in 0.9% MgCl2 solution (Fig. 5) significantly depends on amounts of cross-linking agent.
The analyses of the swelling ability (Figs. 1÷5) indicate that the samples were characterized by lower fluid absorption with increasing amount of cross-linking agent. The system becomes more cross-linked by the presence of cross-links in the structure of the hydrogel, which increases the density of the network. The shorter segments and smaller free spaces are formed which causes the gel absorbs less solvent and stiffens the elastic hydrogel network. Comparing the effect of the ionic strength on the absorbency of absorbents it can be concluded that the presence of fairly strong electrolytes in water causes a loss of swelling ability of gels. The ion exchange between the ions H+ and Na+ occurs in NaCl solution which influences the reduction of the hydrophilic nature of the carboxyl group by the reaction of neutralization. Additionally the significant loss of absorption is caused by the presence of divalent ions in the solution, which also increases the degree of cross-linking of network. Dynamic swelling is associated with the performance of movements in different directions by the external medium placed in hydrogel. The magnetic stirrer induces vortex motions, which increase the intensity of mixing. A particle that is surrounded from all sides by a liquid exhibits a better water absorption capacity and the diffusion of the liquid than in the static swelling. The result is a larger weight of swelling gels.
3.2. Degradation in simulated body fluids
In simulated body fluids observed the phenomenon of progressive degradation what is illustrated in the following : Figure 6. ? degradation in Ringer?s solution (pH=6.66), Figure 7 ? degradation in SBF (pH=7.40), Figure 8 ? degradation in distilled water (pH=6.57).
Degradation of hydrogels is associated with a decrease in molecular weight caused by the rupture of macromolecular chains and the creation of shorter segments, as well as the formation of branched structures, changes in the number and location of bonds. The conducted pH measurements during 42 day incubation period of the samples show the effect of hydrogel on the properties of the fluid in which it is located (Figs 6, 7 and 8). The first thing that draws attention in the analysis of this type of chart is a significant change in pH. In the case of Ringer?s fluid and SBF is it the jump value, while for the citric acid and distilled water decrease is visible. These phenomena are caused by a sudden change of the structure of the hydrogel induced placement of dry gel in a solution. At this stage, the elution of the unreacted acrylic acid, the initiator and the cross-linking agent takes place. This phenomenon occurs for 7 days. From the 7th to the 16th day the decrease of pH values is low, but noticeable. Hydrogel in these days is trying to stabilize the pH of the fluid. Next days, from the 16th to the 42nd day, indicate a slow biodegradation of hydrogels. In this range there are no significant pH jumps. Biodegradation in the SBF is the same as in Ringer?s solution, i.e., without major changes in the pH of the solution. SBF is a buffer with a pH of 7, which includes among others phosphate and sulfate ions, whose presence affects the behavior of the PAA / PEG system. They may cause a sudden decline of pH in the first days of incubation as a result of their settlement on the hydrogel. The samples, which were placed in distilled water, were swelling and this phenomenon could have had an impact on difficulty in estimating the accuracy of the measured values. The results of measurements included in the figures represent the phenomenon of progressive degradation of the hydrogels during the incubation period. In the first step, the rapid jump of pH value is visible, which is due to the systems? aiming to the seventh. Next, the decrease occurs to compensate for pH and a trend to keep this value is visible. The obtained absorbents exhibit compatibility with body fluids. On the basis of figures 6, 7, 8 it can be concluded that more amounts of modifier (PEG) (10% and 15%) is beneficial for the body, because such a hydrogel faster tends to stabilize and compensate of pH, which is present in human body.
3.3. Thermal analysis (TGA)
On the basis of the thermo-gravimetric analysis (Fig. 9) it can be observed, that poly(ethylene glycol) (PEG) is degraded in 90% at 360°C. The addition of PEG increases the thermal resistance of hydrogel matrix in the temperature range to about 250°C.
From the curves for hydrogel, several range of the changes in sample weight can be identified:
I. Water evaporation occurring to 100°C.
II. Slow degradation of the polymer to about 320°C causing 20% weight loss.
III. 15% weight loss in the temperature range 320?410°C.
IV. Complete degradation of the hydrogel; carbonization of the organic master in amount of about 60% of the sample weight.
On the basis of curves it can also be inferred, that the addition of PEG increases the solid residue at 600°C.
The performed investigations showed that the increasing amount of cross-linking agent decreases the swelling capacity of hydrogels. The network structure becomes more dense and thick, contains smaller pores and short chains between cross-linkages. The limited absorption capacity is caused by the presence of PEG in the hydrogel matrix. The modified poly(acrylic) hydrogel has lower swelling ability, but the presence of PEG is beneficial because it enhances the biodegradation processes. In the biological environment conditions the degradation of modifying agent has been observed. In the first stage of incubation, the elution of the unreacted acrylic acid, the initiator and the crosslinking agent occurs. The next days of incubation (after 16, 28, 35 and 42 days) demonstrate that the hydrogel influences beneficially the biological environment. The absorbent affects the stabilization of the pH. After 42 days of incubation it can be concluded that the addition of poly(ethylene glycol) accelerates of the degradation of poly(acrylic) hydrogel. The PAA/PEG hydrogels can be used in future as drug delivery carriers and as advanced wound dressings.
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Translation into English by the Author
Katarzyna BIALIK-WĄS ? M.Sc.,, graduated from the Faculty of Chemical Engineering and Technology, Cracow University of Technology in 2009. Now she is a Ph.D. student in the Department of Chemistry and Technology of Polymers of the Cracow University of Technology. She specializes in preparation of hydrogel materials for biomedical application.
Bożena TYLISZCZAK ? M.Sc.,(Ph.D), graduated from the Faculty of Chemical Engineering and Technology, Cracow University of Technology in 2006. In 2010 she received Ph.D. degree in technical sciences. Now she works in the Department of Chemistry and Technology of Polymers, Cracow University of Technology. Specialization: technology of polymers and biomaterials.
e-mail: email@example.com, phone: +48 12 628 27 47
Edyta WILK ? M.Sc., graduated from the Faculty of Chemical Engineering and Technology, Cracow University of Technology.
Krzysztof PIELICHOWSKI ? Professor (Ph.D., Eng), graduated from the Faculty of Chemical Engineering and Technology, Cracow University of Technology in 1992. He received his Ph.D. degree from AGH ? University of Science and Technology in 1995 and habilitation at Warsaw University of Technology in 1999, and title of Professor in 2006. He is head of the Department of Chemistry and Technology of Polymers, Cracow University of Technology. Specialization: technology of polymers.