Radiation Physics and Chemistry 62 (2001) 107113

Irradiation of polyvinyl alcohol and polyvinyl pyrrolidone

blended hydrogel for wound dressing
Mirzan T. Razzaka,*, Darmawan Darwisb, Zainuddinb, Sukirnoc
a
Center for Utilization of Nuclear Science and Technology, Ministry of Health of the Republic of Indonesia, Jakarta, Indonesia
b
Center for Research and Development of Isotopes and Radiation Technology, Indonesia
c
Ministry of Health of The Republic of Indonesia, Director General of Drug and Food Control, Jakarta, Indonesia

Abstract

Polyvinyl alcohol and polyvinyl pyrrolidone (PVAPVP) blended hydrogel for wound dressing has been prepared by
using gamma rays irradiation technique. The gel fraction, mechanical properties, the water content and water
absorption performance of the hydrogels were measured. It was found that the gel fraction increases with increasing
irradiation dose but never reaches 100% of gel. The PVA/PVP blended hydrogel has a water content in the range
between 60% and 80% and water absorption between 40% and 250%. The water vapor transmission rate value
(WVTR) of the PVA/PVP blended hydrogel varies between 50 and 200 g/m2/h. The hydrogel could be considered as
good barrier against microbes. According to in vitro assessment it was found that the PVA/PVP blended hydrogel was
very useful material that can meet the ecacy requirement and its healing rate was comparable with sterilized gauze and
sofratulle. r 2001 Published by Elsevier Science Ltd.

1. Introduction
Polyvinyl pyrrolidone (PVP) has been used success-
fully as a basic material for the manufacturing of
hydrogel wound dressing (Rosiak, 1991). There are
some commercialized hydrogel wound dressing under
the trade name of Vigilon, Ivalon, Aqua gel an Kik gel
which are all sterilized by using irradiation technique.
Various other types of hydrogel dressing have also been
reported in the literature (Peppas, 1987; Corkhill et al.,
1989; Ohsaki et al., 1991; Kroschwitz, 1992). Polyvinyl
pyrrolidone hydrogel wound dressing was normally
prepared in the presence of agar as a second component
to enhance the mechanical properties of hydrogel. The
present of agar, however, may cause easier penetration
of microorganisms into the hydrogel particularly in a
tropical environment where humidity is high.
Research work on the preparation of hydrogel wound
dressing, which are particularly appropriate to tropical
environment or local requirement are continued (Hilmy
*Corresponding author.
et al., 1993; Jie Chen et al., 1993). For example, Hilmy
et al., 1993 have added polyethylene glycol to the PVP
hydrogel composition. They reported that the presence
of polyethylene glycol could improve the hydrogel
barrier against bacteria.
Instead of using agar as a second component, the
present work reports the preparation of PVP and PVA
blended hydrogel for wound dressing by using gamma
rays irradiation. The gel fraction, mechanical properties,
microbe penetration test, and in vitro assessment were
studied to obtain an applicable hydrogel wound dressing
for tropical environment.
2. Materials and methods
2.1. Materials
PVP with an average molecular weight of 30 kD was
purchased from Fluka AG, Germany. Polyvinyl alcohol
(PVA) with degree of polymerization of 17002400 and
degree of saponication of 99 mol% was supplied by

0969-806X/01/$ - see front matter r 2001 Published by Elsevier Science Ltd.

PII: S 0 9 6 9 - 8 0 6 X ( 0 1 ) 0 0 4 2 7 - 3
108 M.T. Razzak et al. / Radiation Physics and Chemistry 62 (2001) 107113
Kuraray Poval Co. Ltd., Japan. Both polymers were
used without further purication. Other chemicals such
as hematoxylene-eosin (HE), Zoletil 50, Barium sulde
solution and Alcohol were used as received. Solfratulle
(Roussel, England) and Gamma sterilized Gauze were
used for comparison in healing performance. Double-
distilled water was used as solvent.
2.2. Preparation of PVAPVP blended hydrogel
PVA (20 wt%) and PVP (8 wt%) were dissolved in
double-distilled water and heated by using an autoclave
at temperature 1201C and pressure 2 atm for 50 min and
15 min, respectively. The two solutions were mixed with
a composition of 40 parts of PVA and 60 parts of PVP
at temperature of 801C to 901C. The mixed solution was
poured into a plastic mould or plastic bag, sealed and
squeezed between two glass plates and stored overnight
at room temperature. It was then irradiated by gamma-
rays from a cobalt-60 sources with a selected dose and
dose rate at room temperature. The obtained hydrogel
was in c.a. 3 mm thickness.
2.3. Determination of gel fraction
The samples were extracted by water in a Sokhlet
apparatus for 24 h. Then dried to a constant weight in
vacuum. The gel fraction was then calculated gravime-
trically by using the following formula:
Wg
G 100%;
W0
where G is the gel fraction (%), Wg and W0 the weight of
sample after and before extractions, respectively.
2.4. Determination of mechanical properties
Tensile strength and elongation at break were
determined by using the hydrogel specimen which are
cut into dumbbell shape according to ASTM standard
and tested with an instron universal testing instrument
(Strograph-1, Toyoseiki, Model 1122) with a constant
extention rate of 50 mm/min, at room temperature
(301C).
2.5. Determination of equilibrium water content (EWC)
and water absorption
The samples were immersed in water with the
proportional of mass of gels to the mass of water about
1 : 500 at room temperature. Swelling continued to reach
of constant weight of gel. Before weighing the sample,
any surface water was removed with lter paper. The
swelled gel was then slowly dried to the constant weight.
The equilibrium water content (EWC) and the water
absorption were (Aw) calculated as follows:
Ws  Wd
EWC% 100%;
Ws
where Ws and Wd are the weights of swollen state and
dried state respectively;
Ws  W0
AW % 100%;
W0
where Aw is water absorption, and W0 is the weight of
initial gel sample (before being immersed in water).
2.6. Degree of adhesiveness
The degree of adhesiveness of the obtained hydrogel
was measured based on adhesive to aluminum plate by
using Rhesca Tackiness Tester (Rhesca Co. Ltd. Japan)
with a gross weight of 100 gf, a constant extention rate
of 1 mm/min and the pressure time for 30 s at room
temperature.
2.7. Measurement of water vapor transmission rate
The water vapor transmission rate (WVTR) was
measured according to monograph of the European
Pharmacopiae. It consist of measuring the weight loss of
a bottle which contain 25 ml of water. The bottle has a
mouth with a diameter of 35 mm. The hydrogel sample
with a diameter of 40 mm was then put at the bottle
mouth as a cap, and placed in an oven at 351C for 24 h.
The water vapor transmission rate (WVTR) was
calculated by using the following formula:
Wi  Wt
WVTR 106 g=m2 h
A24
where WVTR is expressed in g/m2 h, A is the area of
bottle mouth (mm2), Wi and Wt are the weight of bottle
before and after placed in oven, respectively.
2.8. Microbe penetration test
The gel with a thickness of 23 mm was cut into a size
of 2  2 cm2, put on the TSA (Tryptose Soy Agar) that
had been incubated previously for 18 h at 301C. On the
upper surface of the sample was dropped a suspension of
bacteria (B pumilus, Sarcina lutea, and E. coli) with
concentration of 109/ml and ated by sprayer, then the
sample was incubated at 301C. The observation for
bacterias passing through the hydrogel was done day by
day for 14 days.
2.9. In vitro assessment
In vitro assessment was done by using 28 rabbits
(Japanese white rabbits with an average weight of 2500
3000 g). The procedure of assessment was discussed
 M.T. Razzak et al. / Radiation Physics and Chemistry 62 (2001) 107113 109

previously (Zainuddin et al., 1999). Briey, after

acclimatization for one week the rabbits were cleaned
with barium sulde solution, anesthetized under Zoletil
50 and the epidermis incision was prepared. The sample
of PVA/PVP blended hydrogel was placed in two sites of
wound and was compared to sofratulle and sterile gauze
which are placed at other wound positions. It was then
analyzed for inammatory eect, comfortability and the
absorptions performance of the wound exudate. This
histological observations was also done by using Nikon
Microscope ophtiphot Camera.

3. Results and discussion

3.1. Gel fraction

Irradiation of PVAPVP blended aqueous solution

leads to the formation of insoluble polymer network
(gel). A typical dependence of gel fraction on the Fig. 1. Gel fraction vs. irradiation-dose curve of PVAPVP
irradiation dose is given in Fig. 1. It can be seen that hydrogel.
the gel fraction increases with increasing dose and it
seems never to reach 100% of gel. This certainly
indicates that in the PVAPVP system chain scission
also accompanies the crosslinking. The course of chain
scission is probably due to oxidative degradation as a
result of the presence of residual oxygen. The variation
of the gel fraction at dierence composition of the
polymer blend is not reported.

3.2. Mechanical properties

The tensile strength and elongation at break of PVA

PVP blended hydrogel are measured. The results are
shown in Fig. 2. Both tensile strength and elongation at
break increase with increasing of dose and then decrease.
The increase of the tensile strength was believed due to
cross-linking. But, the increase of elongation at break
may be explained as the eect of grafted chain that
occurred simultaneously with crosslinking (Matsuda
et al., 1961). As can be seen in Fig. 2, the tensile
strength of 15  104 kg/cm2 and elongation at break
175% were achieved at irradiation condition of 20 kGy.
Fig. 2. Tensile strenght (TB) and elongation at break (EB) o.
These values are enough to fulll the mechanical
properties required for wound dressing.

3.3. Water content and water absorption

As shown in Table 1 it was observed that the water
content of PVAPVP blended hydrogel tends to increase
with increasing PVP concentration, but in turn reduces
the water absorption. This fact is certainly under-
standable because if the initial water content of the
same sample increases then the ability of the sample to
absorb more water will become lower. The PVAPVP
blended hydrogels show the water content to be in the
range between 60% and 80% and water absorption (24 h
immersed in water) between 40% and 250% (Table 1).
Even though the obtained PVAPVP blended hydro-
gel had an enough amount of water content, but in fact
it can absorb more water. The absorption of water, by
the hydrogel blend is much also depend on irradiation
dose. The relationship between water absorption and the
time of immersion for dierent doses are shown in Fig 3.
It can be seen in Fig 3, that the higher the irradiation
110 M.T. Razzak et al. / Radiation Physics and Chemistry 62 (2001) 107113

Table 1
The water content, water absorption and water vapor
transmission rate of dierent composition of PVAPVP
blended hydogel.

PVP Composition Water content Water abs. WVTR

conc. (%) PVA : PVP (EWC) (%) (%) in 24 h (g/m2/h)
immersion
time

4 40:60 67.19 42 89.64

70:30 65.45 125 100.9
90:10 62.46 247 110.20

6 40:60 75.01 95 173.97

70:30 77.30 127 126.49
90:10 65.07 168 139.10

8 40:60 78.00 139 139.28

70:30 75.43 164 164.96
90:10 F Sample lost F

10 40:60 78.30 94 156.76

70:30 76.82 109 118.45
90:10 68.07 160 138.90 Fig. 3. Relationship between water absorption (%) and im-
mersion time (h) at dierent irradiation dose.
12 40:60 79.06 105 150.60
70:30 77.50 117 131.39
90:10 75.00 167 129.40

Table 2
The relationship between the water content and adhesiveness
dose, the lower the water absorption. This is because the PVP Water Adhesiveness
cross-linking will be higher at a higher dose. The concentration content (gt)
absorption of water will be sharply higher at the % w/w (EWC) (%)
immersion time of less than 5 h. Whereas at more than
5 h immersion time, the rate of absorption will be only 2.4 89.5 6
3.6 88.2 7
slowly increased.
4.8 87.1 9
The adhesiveness of PVAPVP blended hydrogel 6.0 85.6 10
depended on the concentration of PVP in the hydrogel. 7.2 74.7 12
The higher PVP concentration, however aects the
decreases of water content but is signicantly increases
of adhesiveness as shown in Table 2. The phenomenon
can be explained that the higher PVP concentration will
increase the cross-linking therefore decreases water maintaining the high humidity in the wound area, in
content, but at the same time the functional group order to accelerate the formation of granule and
contributed from PVP will also increases which causes epitelesation process. Based on Table 1, it can be seen
the improvement in adhesiveness. that the WVTR values of PVAPVP blended hydrogel
are around 80200 g/m2/h. These values seem to be in an
3.4. Water vapor transmission rate (WVTR) ideal range for wound dressing. A higher value of
WVTR causes a faster drying of the wound. Though
According to Peppas et al., 1987, the most dicult there is not an exact ideal value of WVTR for wound
problem in taking care of the burned victim was the fact dressing, the value must not be so high because it will
that the victim may have lost most of their body liquid cause a dry condition in the wound area. On the other
due to evaporation and exudation. These will aect the hand, if the WVTR value is so low, then it will make the
decrease of body temperature and accelerate the rate of accumulation of exudates which may cause the decelera-
metabolism. Therefore, the hydrogel wound dressing tion of healing process and opens up the risk of bacterial
must avoid or at least reduce the body liquid lost i.e. by growth. For comparison, Table 3 shows WVTR for
controlling absorption and transmission as well as by some commercial wound dressing values (Bruin et al.,
 M.T. Razzak et al. / Radiation Physics and Chemistry 62 (2001) 107113
Table 3
The value of WVTR of some commercialized wound dressing
Wound dressing types WVTR (g/m2/hr)
Biabrone 154
Metalline 53
Op site 33
Omiderm 208
Human skin (we) 15
Pig skin (we) 9
1990). According to Bruin et al., 1990, an occlusive
wound covering, such as Op Site (see Table 3) with a
WVTR of 33 g/m2/h, has a weakness point, i.e. it causes
an accumulation of exudates under the covering and in
turn causes infection.
3.5. Microbe penetration test
Based on the microbe penetration test, there were no
bacterias passing through the hydrogel during day by
day observation for 14 days. Since no bacteria was
found on the TSA medium, the PVAPVP blended
hydrogel could be considered as a good barrier against
the microbes. This characteristic is very important for
hydrogel dressing, especially in protecting the wound
from further infection so that it may accelerate the
healing of wound.
3.6. In vitro assessment
The macroscopic observations of the wound healing
eect in terms of comfortability and the excudate
absorption performance of the hydrogel sample as
compared to Sofratulle and Sterilized Gauze were done.
It was found that the PVAPVP blended hydrogel and
Sofratulle have a better comfortability than that of the
sterilized gauze when dressing are removed from the
wound. The hydrogel adhered slightly to the wound and
caused only a little hemorphagic. The capability of
the PVAPVP blended hydrogel in absorbing wound
exudates was observed as high as the Sterilized Gauze,
while Sofratulle nearly did not absorb any exudates.
Furthermore the PVAPVP blended hydrogel was better
in preventing the wound from contamination compared
with the sterilized gauze and sofratulle. This is possible
because it has a good comfortability which are enable to
cover the wound perfectly. It can be seen in Fig. 4, that
the healing process which are reected by the reduction
of the wound surface area seems to be proceeded quite
fast up to 10 days, then it will be slowly until the wound
was fully recovered at the day of 18. There were no
signicant dierence on the time of complete recovering
of the wound. However the surface of recovered wound
111
Fig. 4. Relationship between the mean surface area of the
wound.
treated with PVAPVP blended hydrogel or sofratulle
were observed smoother than that of treated with
sterilized gauze.
Histological study was done by microscopical ob-
servation of the wound healing process. Microscopical
observation of the formation of the new tissue at day 3,
7, 14 and 18 revealed that at day 3, the wound show no
hair follicle and no sebaceous gland under the wound
surface (see Fig. 5). The wound surface was covered by
exudates layer which was consisted of the mixture of the
brin, tissue debris and polymorpho nuclear cell (PMN).
The tissue bond underwent oidema (macrophage) and
blood vessel look hyperemis. Besides that, the initial
granulation started to be formed. There were no bacteria
of fungi colonies found. At day 7, all wounds either
tested with PVA/PVP blended hydrogel, sofratulle or
sterilized gauze showed a signicant inammatory
reaction.
At the day 14, although the wound healing was almost
completely achieved and granulation tissue has been
formed, the wound surface were still covered by PMA
exudates (see Fig. 6). The epidermis did not yet contain
hair follicle and sebaceous gland, and the edge of the
wound became thicker due to proliferation of the epitel
cells. These macroscopic and microscopic observation
under in vitro assessment revels that the PVAPVP
blended hydrogel can meet the ecacy requirement and
its healing rate was comparable to that Sterile Gauze
and Sofratulle. The hydrogel was also pleasant fell,
comfortable, and does not disturb the formation of cells
and new tissue on the skin.
112 M.T. Razzak et al. / Radiation Physics and Chemistry 62 (2001) 107113

Fig. 5. Histology of wound after 3 days of treatment with PVAPVP blended hydrogel: (a) the wound covered by brin, debris and
PMN exudate, (b) hair follicles undergo degeneration and integration. Magnication: 40  .

Fig. 6. Histology of wound after 14 days of treatment with PVAPVP blended hydrogel. Epidermis layer undergoes proliferation (a)
and information of dermis tissue bond which is consisted of PMN, eosinol and macrophage (b). Magnication: 40  .

4. Conclusion pleasant in touch and painless in removal, exhibit high

elasticity but also good mechanical strength, good
The PVAPVP blended hydrogel shows some proper- transparency and can act as a barrier against the
ties which can meet the requirements of an ideal wound microbes. This hydrogel wound dressing is highly
dressing. For example, its absorb eectively the uid, potential to be used in tropical environment.
 M.T. Razzak et al. / Radiation Physics and Chemistry 62 (2001) 107113
Acknowledgements
The author wish to thank Prof. Dr. J.M. Rosiak and
Dr. Nazly Hilmy, PhD, for their valuable suggestion.
The authors also would like appreciate Dr. Iwan
Budiarso for his valuable discussion for in vitro
assessment. Assistant to experiment by Ms. Dewi SP,
Ms. Yuharni, Ida and Rachmi are also acknowledged.
This research work is partially supported by IAEA
under a Research Contract No. 8978/R2/DPA.
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