- Email: [email protected]
Use of electron beam for the production of hydrogel dressings
ARTICLE IN PRESS
Radiation Physics and Chemistry 77 (2008) 200–202 www.elsevier.com/locate/radphyschem
Short communication
Use of electron beam for the production of hydrogel dressings Z. Ajjia,, G. Mirjalilib, A. Alkhataba, H. Dadaa a
Polymer Technology Division, Department of Radiation Technology, Atomic Energy Commission of Syria, P.O. Box 6091, Damascus, Syria b Yazd Radiation Processing Center, P.O. Box 89175-389, Yazd, Iran Received 7 February 2007; accepted 27 May 2007
Abstract The electron beam irradiation technique has been utilized to prepare hydrogel wound dressings. The composition of the dressings is based on polyvinylpyrrolidone (PVP), poly(ethylene glycol) (PEG), and agar. Increasing the irradiation dose leads to an increase in the gel fraction; this increase is due to increased crosslink density. The gel fraction% decreases as the PEG concentration increases. The maximum swelling% decreases with increasing the irradiation dose, but increases with increasing the PEG concentration. This relationship can be utilized to modify the gel properties as gel fraction% and maximum swelling of the hydrogel. The prepared dressings could be considered as a good barrier against microbes. r 2007 Elsevier Ltd. All rights reserved. Keywords: Hydrogel; Polyvinylpyrrolidone; Poly(ethylene glycol); Agar; Electron beam
1. Introduction Hydrogels are three-dimensional crosslinked hydrophilic polymers, which are able to swell in liquids. Polyvinylpyrrolidone (PVP) has been used successfully as a basic material for the preparation of hydrogel wound dressings (Rosiak et al., 1989; Rosiak, 1991). They are usually good biocompatible and widely applied, not only as wound dressings but also as drug delivery systems (Lugao et al., 1998). Various hydrogel wound dressings, which are sterilized using radiation are already there in the market (Razzak et al., 2001). Dressings based on PVP are normally prepared in the presence of agar and poly(ethylene glycol) (PEG); the addition of PEG to the composition could improve the ability of the dressing as barrier against bacteria (Hilmy et al., 1993). An ideal dressing should meet some requirements as absorbing fluids effectively, pleasant in touch and painless in removal, exhibition of high elasticity but also good mechanical strength, and can act as a barrier against the microbes. The present work reports the use of the electron accelerator (Rhodotron TT200) for preparation of hydrogel Corresponding author.
E-mail address: [email protected] (Z. Ajji). 0969-806X/$ - see front matter r 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.radphyschem.2007.05.016
dressings, and to demonstrate the radiation production technique of hydrogel dressings to the Radiation Processing Center in Yazd, Iran. The effect of some parameters on the properties of the dressing was investigated as: gel fraction and maximum swelling. 2. Experimental The hydrogel wound dressings were composed of PVP (BASF, MW ¼ 90000), PEG (BASF, MW ¼ 200), agar (Difco) and water. The first step of manufacturing is the preparation of aqueous solution of dressing’s components. After dissolving and mixing them at elevated temperature, a homogenous solution was formed. Then the molds, which can also be used as final packages, were filled with the solution of the dressing. After cooling down, the solution becomes physically solid gels (high viscous), which then are packed in the proper final boxes. The solid gels (in the packages) were finally exposed to ionizing radiation to become crosslinked. An electron accelerator (Rhodotron TT200) was used for the irradiation; the beam energy is E10 MeV and the dose rate was 600 kGy/min. An irradiation dose of 25 kGy has to be applied usually according to international requirements to ensure sterility of the product.
ARTICLE IN PRESS Z. Ajji et al. / Radiation Physics and Chemistry 77 (2008) 200–202
3. Results and discussion 0
2
201
PEG Concentration% 4 6 8
10
2100
3.1. Gel fraction
swelling% vs. PEG%
1950 Maximum swelling%
Fig. 1 represents the gel fraction% vs. the irradiation dose (PVP concentration ¼ 8%) and the PEG concentration (dose ¼ 25 kGy). It can be seen that the gel fraction% increases with increasing the irradiation dose. This is maybe due to the increase in the crosslink degree with increasing the irradiation dose (Bodugo¨z et al., 1999). The gel fraction is generally lower than that obtained using gamma irradiation (Ajji et al., 2005). This is maybe due to the very high dose rate (600 kGy/min) compared with the 6 kGy/h for the gamma facility used previously. It can also be seen that the increase in the PEG concentration reduces the gel fraction%, which goes down to 22% when the PEG concentration becomes 10%. The PEG does not only act as a plasticizer, but it also reduces the crosslinking reaction and consequently the gelation process. PEG as an alcohol may act as a radical scavenger (Lugao et al., 1998), and this effect can be utilized to modify (increase or reduce) the gel fraction% of the prepared hydrogel according to the irradiation dose.
2200 2100
1800 2000 1650
1900
1500
1800 Swelling% vs. dose
1350
1700 15
20 25 30 Irradiation dose [kGy]
35
40
Fig. 2. Maximum swelling of the hydrogel dressings vs. the irradiation dose (PVP ¼ 8%) and the PEG concentration (irradiation dose ¼ 25 kGy).
1400 1200
3.2. Maximum swelling% The maximum swelling% of the prepared hydrogel dressings is represented in Fig. 2 vs. the irradiation dose (PVP ¼ 8%) and the PEG concentration (irradiation dose ¼ 25 kGy). The maximum swelling decreases with increasing the irradiation dose; this is maybe due to an increase in the crosslinking degree. The increase in the maximum swelling with respect to the increase in the PEG concentration can be explained with a reduced crosslink density due to the presence of PEG; this influence is contrary to the influence of the irradiation dose.
2 76
4
PEG Concentration% 6 8
800 600 400 14.4 kGy
200
28.8 kGy 38.4 kGy
0 0
20
40 Time [h]
60
80
Fig. 3. Swelling kinetics of the hydrogel dressings vs. the time (for different doses).
10
Gel% vs. PEG%
Swelling%
1000
70
74 60
Gelation%
72 70
50
68 66
40
64 30
62 60
20
Gel% vs.dose
58 10
15
20 25 30 Irradiation dose [kGy]
Fig. 3 represents the swelling% of the hydrogel dressings with the time for different irradiation doses. It can be seen that all hydrogels reaches the equilibrium swelling after almost 1 day of soaking. At the first stage of the curves, the swelling rate is very high, and water can penetrate easily into the polymer network; the swelling rate is almost similar in the fist stage independent of the irradiation dose. These results are comparable with the data of the Brazilian dressings (Lugao et al., 1998).
35
40
Fig. 1. Gel fraction% of the dressings vs. the irradiation dose (PVP ¼ 8%) and the PEG concentration (irradiation dose ¼ 25 kGy).
3.3. Isothermal dehydration The dehydration behavior was followed by measuring the percent decrease of the mass of the dressing isothermally at 37 1C using a Mettler TG50-thermobalance,
ARTICLE IN PRESS Z. Ajji et al. / Radiation Physics and Chemistry 77 (2008) 200–202
202
100 10kGy 20kGy 40kGy
Weight loss%
80
This characteristic is important, especially, in protecting the wound from further infection so that it may accelerate the healing of wound. 4. Conclusion
60
40
20
0 0
20
40
60
80 100 120 Time [min]
140
160
180
Fig. 4. Dehydration of the hydrogel dressings vs. the time for different irradiation doses.
within nitrogen in order to simulate the use of the dressing on wounded skin (Fig. 4). It can be seen that the relative rate of dehydration decreases with increasing the irradiation dose. This is maybe due to increased crosslinking degree with increasing the irradiation dose. The residual mass is directly dependant on the concentration of solid material in the sample, which is also observed previously by Lugao et al. (1998). 3.4. Microbe penetration test Gram-negative bacteria (Escherichia coli) were used to carry out the microbe penetration test. The upper surface of the dressings was contaminated with the microbe solution, and then the sample was incubated at 37 1C for 24 h. The test showed that the bacteria did not pass through the hydrogel dressing. Thus the hydrogel dressings could be considered as a barrier against the microbes.
Electron accelerator was utilized to prepare hydrogel wound dressings composed of PVP, PEG, and agar. Various process parameters have been investigated to fit the hydrogel properties. The gel fraction% increases with increasing the irradiation dose, but decreases with increasing PEG. The maximum swelling% decreases with increasing the irradiation dose, but increases with increasing the PEG concentration. PEG plays an important role to modify the gel fraction% and maximum swelling% according to the irradiation dose. The prepared dressings could also be considered as good barrier against microbes. References Ajji, Z., Rosiak, J.M., Othman, I., 2005. Production of hydrogel wound dressings using Gamma radiation. Nucl. Instrum. Methods Phys. Res. B 229, 375–380. Bodugo¨z, H., Pekel, N., Gu¨ven, O., 1999. Preparation of poly(vinyl alcohol) hydrogels with radiation grafted citric and succinic acid groups. Radiat. Phys. Chem. 55 (5–6), 667–671. Hilmy, N., Darwis, D., Hardiningsih, L., 1993. Poly(N-vinylpyrrolidone) hydrogels: 2. hydrogel composites as wound dressing for tropical environment. Radiat. Phys. Chem. 42 (4–6), 911–914. Lugao, A.B., Machado, L.D.B., Miranda, L.F., Alvarez, M.R., Rosiak, J.M., 1998. Study of wound dressing structure and hydration/ dehydration properties. Radiat. Phys. Chem. 52 (1–6), 319–322. Razzak, M.T., Darwis, D., Zainuddin, S., 2001. Irradiation of polyvinyl alcohol and polyvinyl pyrrolidone blended hydrogel for wound dressing. Radiat. Phys. Chem. 62 (1), 107–113. Rosiak, J.M., 1991. Hydrogel dressing, radiation effects on polymers. In: Clough, R.L., Shalaby, S.W. (Eds.), ACS Book Series, Washington, DC, 475pp. Rosiak, J.M., Rucinska-Reybas, A., Pekala, W., 1989. US Patent No. 4, 871, 490, Method of Manufacturing of Hydrogel Dressings.
Radiation Physics and Chemistry 77 (2008) 200–202 www.elsevier.com/locate/radphyschem
Short communication
Use of electron beam for the production of hydrogel dressings Z. Ajjia,, G. Mirjalilib, A. Alkhataba, H. Dadaa a
Polymer Technology Division, Department of Radiation Technology, Atomic Energy Commission of Syria, P.O. Box 6091, Damascus, Syria b Yazd Radiation Processing Center, P.O. Box 89175-389, Yazd, Iran Received 7 February 2007; accepted 27 May 2007
Abstract The electron beam irradiation technique has been utilized to prepare hydrogel wound dressings. The composition of the dressings is based on polyvinylpyrrolidone (PVP), poly(ethylene glycol) (PEG), and agar. Increasing the irradiation dose leads to an increase in the gel fraction; this increase is due to increased crosslink density. The gel fraction% decreases as the PEG concentration increases. The maximum swelling% decreases with increasing the irradiation dose, but increases with increasing the PEG concentration. This relationship can be utilized to modify the gel properties as gel fraction% and maximum swelling of the hydrogel. The prepared dressings could be considered as a good barrier against microbes. r 2007 Elsevier Ltd. All rights reserved. Keywords: Hydrogel; Polyvinylpyrrolidone; Poly(ethylene glycol); Agar; Electron beam
1. Introduction Hydrogels are three-dimensional crosslinked hydrophilic polymers, which are able to swell in liquids. Polyvinylpyrrolidone (PVP) has been used successfully as a basic material for the preparation of hydrogel wound dressings (Rosiak et al., 1989; Rosiak, 1991). They are usually good biocompatible and widely applied, not only as wound dressings but also as drug delivery systems (Lugao et al., 1998). Various hydrogel wound dressings, which are sterilized using radiation are already there in the market (Razzak et al., 2001). Dressings based on PVP are normally prepared in the presence of agar and poly(ethylene glycol) (PEG); the addition of PEG to the composition could improve the ability of the dressing as barrier against bacteria (Hilmy et al., 1993). An ideal dressing should meet some requirements as absorbing fluids effectively, pleasant in touch and painless in removal, exhibition of high elasticity but also good mechanical strength, and can act as a barrier against the microbes. The present work reports the use of the electron accelerator (Rhodotron TT200) for preparation of hydrogel Corresponding author.
E-mail address: [email protected] (Z. Ajji). 0969-806X/$ - see front matter r 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.radphyschem.2007.05.016
dressings, and to demonstrate the radiation production technique of hydrogel dressings to the Radiation Processing Center in Yazd, Iran. The effect of some parameters on the properties of the dressing was investigated as: gel fraction and maximum swelling. 2. Experimental The hydrogel wound dressings were composed of PVP (BASF, MW ¼ 90000), PEG (BASF, MW ¼ 200), agar (Difco) and water. The first step of manufacturing is the preparation of aqueous solution of dressing’s components. After dissolving and mixing them at elevated temperature, a homogenous solution was formed. Then the molds, which can also be used as final packages, were filled with the solution of the dressing. After cooling down, the solution becomes physically solid gels (high viscous), which then are packed in the proper final boxes. The solid gels (in the packages) were finally exposed to ionizing radiation to become crosslinked. An electron accelerator (Rhodotron TT200) was used for the irradiation; the beam energy is E10 MeV and the dose rate was 600 kGy/min. An irradiation dose of 25 kGy has to be applied usually according to international requirements to ensure sterility of the product.
ARTICLE IN PRESS Z. Ajji et al. / Radiation Physics and Chemistry 77 (2008) 200–202
3. Results and discussion 0
2
201
PEG Concentration% 4 6 8
10
2100
3.1. Gel fraction
swelling% vs. PEG%
1950 Maximum swelling%
Fig. 1 represents the gel fraction% vs. the irradiation dose (PVP concentration ¼ 8%) and the PEG concentration (dose ¼ 25 kGy). It can be seen that the gel fraction% increases with increasing the irradiation dose. This is maybe due to the increase in the crosslink degree with increasing the irradiation dose (Bodugo¨z et al., 1999). The gel fraction is generally lower than that obtained using gamma irradiation (Ajji et al., 2005). This is maybe due to the very high dose rate (600 kGy/min) compared with the 6 kGy/h for the gamma facility used previously. It can also be seen that the increase in the PEG concentration reduces the gel fraction%, which goes down to 22% when the PEG concentration becomes 10%. The PEG does not only act as a plasticizer, but it also reduces the crosslinking reaction and consequently the gelation process. PEG as an alcohol may act as a radical scavenger (Lugao et al., 1998), and this effect can be utilized to modify (increase or reduce) the gel fraction% of the prepared hydrogel according to the irradiation dose.
2200 2100
1800 2000 1650
1900
1500
1800 Swelling% vs. dose
1350
1700 15
20 25 30 Irradiation dose [kGy]
35
40
Fig. 2. Maximum swelling of the hydrogel dressings vs. the irradiation dose (PVP ¼ 8%) and the PEG concentration (irradiation dose ¼ 25 kGy).
1400 1200
3.2. Maximum swelling% The maximum swelling% of the prepared hydrogel dressings is represented in Fig. 2 vs. the irradiation dose (PVP ¼ 8%) and the PEG concentration (irradiation dose ¼ 25 kGy). The maximum swelling decreases with increasing the irradiation dose; this is maybe due to an increase in the crosslinking degree. The increase in the maximum swelling with respect to the increase in the PEG concentration can be explained with a reduced crosslink density due to the presence of PEG; this influence is contrary to the influence of the irradiation dose.
2 76
4
PEG Concentration% 6 8
800 600 400 14.4 kGy
200
28.8 kGy 38.4 kGy
0 0
20
40 Time [h]
60
80
Fig. 3. Swelling kinetics of the hydrogel dressings vs. the time (for different doses).
10
Gel% vs. PEG%
Swelling%
1000
70
74 60
Gelation%
72 70
50
68 66
40
64 30
62 60
20
Gel% vs.dose
58 10
15
20 25 30 Irradiation dose [kGy]
Fig. 3 represents the swelling% of the hydrogel dressings with the time for different irradiation doses. It can be seen that all hydrogels reaches the equilibrium swelling after almost 1 day of soaking. At the first stage of the curves, the swelling rate is very high, and water can penetrate easily into the polymer network; the swelling rate is almost similar in the fist stage independent of the irradiation dose. These results are comparable with the data of the Brazilian dressings (Lugao et al., 1998).
35
40
Fig. 1. Gel fraction% of the dressings vs. the irradiation dose (PVP ¼ 8%) and the PEG concentration (irradiation dose ¼ 25 kGy).
3.3. Isothermal dehydration The dehydration behavior was followed by measuring the percent decrease of the mass of the dressing isothermally at 37 1C using a Mettler TG50-thermobalance,
ARTICLE IN PRESS Z. Ajji et al. / Radiation Physics and Chemistry 77 (2008) 200–202
202
100 10kGy 20kGy 40kGy
Weight loss%
80
This characteristic is important, especially, in protecting the wound from further infection so that it may accelerate the healing of wound. 4. Conclusion
60
40
20
0 0
20
40
60
80 100 120 Time [min]
140
160
180
Fig. 4. Dehydration of the hydrogel dressings vs. the time for different irradiation doses.
within nitrogen in order to simulate the use of the dressing on wounded skin (Fig. 4). It can be seen that the relative rate of dehydration decreases with increasing the irradiation dose. This is maybe due to increased crosslinking degree with increasing the irradiation dose. The residual mass is directly dependant on the concentration of solid material in the sample, which is also observed previously by Lugao et al. (1998). 3.4. Microbe penetration test Gram-negative bacteria (Escherichia coli) were used to carry out the microbe penetration test. The upper surface of the dressings was contaminated with the microbe solution, and then the sample was incubated at 37 1C for 24 h. The test showed that the bacteria did not pass through the hydrogel dressing. Thus the hydrogel dressings could be considered as a barrier against the microbes.
Electron accelerator was utilized to prepare hydrogel wound dressings composed of PVP, PEG, and agar. Various process parameters have been investigated to fit the hydrogel properties. The gel fraction% increases with increasing the irradiation dose, but decreases with increasing PEG. The maximum swelling% decreases with increasing the irradiation dose, but increases with increasing the PEG concentration. PEG plays an important role to modify the gel fraction% and maximum swelling% according to the irradiation dose. The prepared dressings could also be considered as good barrier against microbes. References Ajji, Z., Rosiak, J.M., Othman, I., 2005. Production of hydrogel wound dressings using Gamma radiation. Nucl. Instrum. Methods Phys. Res. B 229, 375–380. Bodugo¨z, H., Pekel, N., Gu¨ven, O., 1999. Preparation of poly(vinyl alcohol) hydrogels with radiation grafted citric and succinic acid groups. Radiat. Phys. Chem. 55 (5–6), 667–671. Hilmy, N., Darwis, D., Hardiningsih, L., 1993. Poly(N-vinylpyrrolidone) hydrogels: 2. hydrogel composites as wound dressing for tropical environment. Radiat. Phys. Chem. 42 (4–6), 911–914. Lugao, A.B., Machado, L.D.B., Miranda, L.F., Alvarez, M.R., Rosiak, J.M., 1998. Study of wound dressing structure and hydration/ dehydration properties. Radiat. Phys. Chem. 52 (1–6), 319–322. Razzak, M.T., Darwis, D., Zainuddin, S., 2001. Irradiation of polyvinyl alcohol and polyvinyl pyrrolidone blended hydrogel for wound dressing. Radiat. Phys. Chem. 62 (1), 107–113. Rosiak, J.M., 1991. Hydrogel dressing, radiation effects on polymers. In: Clough, R.L., Shalaby, S.W. (Eds.), ACS Book Series, Washington, DC, 475pp. Rosiak, J.M., Rucinska-Reybas, A., Pekala, W., 1989. US Patent No. 4, 871, 490, Method of Manufacturing of Hydrogel Dressings.