Radiation Physics and Chemistry 62 (2001) 107–113

Irradiation of polyvinyl alcohol and polyvinyl pyrrolidoneblended hydrogel for wound dressing

Mirzan T. Razzaka,*, Darmawan Darwisb, Zainuddinb, Sukirnoc

aCenter for Utilization of Nuclear Science and Technology, Ministry of Health of the Republic of Indonesia, Jakarta, IndonesiabCenter for Research and Development of Isotopes and Radiation Technology, Indonesia

cMinistry of Health of The Republic of Indonesia, Director General of Drug and Food Control, Jakarta, Indonesia

Abstract

Polyvinyl alcohol and polyvinyl pyrrolidone (PVA–PVP) blended hydrogel for wound dressing has been prepared byusing 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 increasingirradiation dose but never reaches 100% of gel. The PVA/PVP blended hydrogel has a water content in the rangebetween 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 asgood barrier against microbes. According to in vitro assessment it was found that the PVA/PVP blended hydrogel wasvery useful material that can meet the efficacy 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 aresome commercialized hydrogel wound dressing underthe 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 beenreported in the literature (Peppas, 1987; Corkhill et al.,1989; Ohsaki et al., 1991; Kroschwitz, 1992). Polyvinyl

pyrrolidone hydrogel wound dressing was normallyprepared in the presence of agar as a second componentto enhance the mechanical properties of hydrogel. The

present of agar, however, may cause easier penetrationof microorganisms into the hydrogel particularly in atropical environment where humidity is high.

Research work on the preparation of hydrogel wounddressing, which are particularly appropriate to tropicalenvironment or local requirement are continued (Hilmy

et al., 1993; Jie Chen et al., 1993). For example, Hilmy

et al., 1993 have added polyethylene glycol to the PVPhydrogel composition. They reported that the presenceof 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 gammarays irradiation. The gel fraction, mechanical properties,microbe penetration test, and in vitro assessment werestudied 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 waspurchased from Fluka AG, Germany. Polyvinyl alcohol

(PVA) with degree of polymerization of 1700–2400 anddegree of saponification of 99mol% was supplied by*Corresponding author.

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

Kuraray Poval Co. Ltd., Japan. Both polymers wereused without further purification. Other chemicals such

as hematoxylene-eosin (HE), Zoletil 50, Barium sulfidesolution 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 PVA–PVP blended hydrogel

PVA (20wt%) and PVP (8wt%) were dissolved indouble-distilled water and heated by using an autoclave

at temperature 1201C and pressure 2 atm for 50min and15min, respectively. The two solutions were mixed witha composition of 40 parts of PVA and 60 parts of PVP

at temperature of 801C to 901C. The mixed solution waspoured into a plastic mould or plastic bag, sealed andsqueezed between two glass plates and stored overnightat room temperature. It was then irradiated by gamma-

rays from a cobalt-60 sources with a selected dose anddose rate at room temperature. The obtained hydrogelwas in c.a. 3mm 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 invacuum. The gel fraction was then calculated gravime-trically by using the following formula:

G ¼Wg

W0�100%;

where G is the gel fraction (%),Wg andW0 the weight ofsample after and before extractions, respectively.

2.4. Determination of mechanical properties

Tensile strength and elongation at break weredetermined by using the hydrogel specimen which are

cut into dumbbell shape according to ASTM standardand tested with an instron universal testing instrument(Strograph-1, Toyoseiki, Model 1122) with a constant

extention rate of 50mm/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 about1 : 500 at room temperature. Swelling continued to reachof constant weight of gel. Before weighing the sample,

any surface water was removed with filter paper. Theswelled gel was then slowly dried to the constant weight.

The equilibrium water content (EWC) and the waterabsorption were (Aw) calculated as follows:

EWCð%Þ ¼Ws �Wd

Ws�100%;

where Ws and Wd are the weights of swollen state anddried state respectively;

AWð%Þ ¼ðWs �W0Þ

W0�100%;

where Aw is water absorption, and W0 is the weight ofinitial gel sample (before being immersed in water).

2.6. Degree of adhesiveness

The degree of adhesiveness of the obtained hydrogelwas measured based on adhesive to aluminum plate byusing Rhesca Tackiness Tester (Rhesca Co. Ltd. Japan)

with a gross weight of 100 gf, a constant extention rateof 1mm/min and the pressure time for 30 s at roomtemperature.

2.7. Measurement of water vapor transmission rate

The water vapor transmission rate (WVTR) wasmeasured according to monograph of the EuropeanPharmacopiae. It consist of measuring the weight loss of

a bottle which contain 25ml of water. The bottle has amouth with a diameter of 35mm. The hydrogel samplewith a diameter of 40mm 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) wascalculated by using the following formula:

WVTR ¼ðWi �WtÞA�24

�106 g=m2 h

where WVTR is expressed in g/m2 h, A is the area ofbottle mouth (mm2),Wi andWt are the weight of bottlebefore and after placed in oven, respectively.

2.8. Microbe penetration test

The gel with a thickness of 2–3mm was cut into a sizeof 2� 2 cm2, put on the TSA (Tryptose Soy Agar) that

had been incubated previously for 18 h at 301C. On theupper surface of the sample was dropped a suspension ofbacteria (B pumilus, Sarcina lutea, and E. coli) with

concentration of 109/ml and flated by sprayer, then thesample was incubated at 301C. The observation forbacteria’s passing through the hydrogel was done day byday 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) 107–113108

previously (Zainuddin et al., 1999). Briefly, afteracclimatization for one week the rabbits were cleaned

with barium sulfide solution, anesthetized under Zoletil50 and the epidermis incision was prepared. The sampleof PVA/PVP blended hydrogel was placed in two sites of

wound and was compared to sofratulle and sterile gauzewhich are placed at other wound positions. It was thenanalyzed for inflammatory effect, comfortability and theabsorptions performance of the wound exudate. This

histological observations was also done by using NikonMicroscope ophtiphot Camera.

3. Results and discussion

3.1. Gel fraction

Irradiation of PVA–PVP blended aqueous solution

leads to the formation of insoluble polymer network(gel). A typical dependence of gel fraction on theirradiation dose is given in Fig. 1. It can be seen thatthe gel fraction increases with increasing dose and it

seems never to reach 100% of gel. This certainlyindicates that in the PVA–PVP system chain scissionalso accompanies the crosslinking. The course of chain

scission is probably due to oxidative degradation as aresult of the presence of residual oxygen. The variationof the gel fraction at difference 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 areshown 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 tocross-linking. But, the increase of elongation at break

may be explained as the effect of grafted chain thatoccurred simultaneously with crosslinking (Matsudaet al., 1961). As can be seen in Fig. 2, the tensile

strength of 15� 10�4 kg/cm2 and elongation at break175% were achieved at irradiation condition of 20 kGy.These values are enough to fulfill the mechanicalproperties required for wound dressing.

3.3. Water content and water absorption

As shown in Table 1 it was observed that the watercontent of PVA–PVP blended hydrogel tends to increasewith increasing PVP concentration, but in turn reduces

the water absorption. This fact is certainly under-standable because if the initial water content of thesame sample increases then the ability of the sample to

absorb more water will become lower. The PVA–PVPblended 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 PVA–PVP blended hydro-

gel had an enough amount of water content, but in fact

it can absorb more water. The absorption of water, bythe hydrogel blend is much also depend on irradiationdose. The relationship between water absorption and thetime of immersion for different doses are shown in Fig 3.

It can be seen in Fig 3, that the higher the irradiation

Fig. 1. Gel fraction vs. irradiation-dose curve of PVA–PVP

hydrogel.

Fig. 2. Tensile strenght (TB) and elongation at break (EB) off.

M.T. Razzak et al. / Radiation Physics and Chemistry 62 (2001) 107–113 109

dose, the lower the water absorption. This is because thecross-linking will be higher at a higher dose. Theabsorption of water will be sharply higher at the

immersion time of less than 5 h. Whereas at more than5 h immersion time, the rate of absorption will be onlyslowly increased.

The adhesiveness of PVA–PVP blended hydrogeldepended on the concentration of PVP in the hydrogel.The higher PVP concentration, however affects the

decreases of water content but is significantly increasesof adhesiveness as shown in Table 2. The phenomenoncan be explained that the higher PVP concentration will

increase the cross-linking therefore decreases watercontent, but at the same time the functional groupcontributed from PVP will also increases which causesthe improvement in adhesiveness.

3.4. Water vapor transmission rate (WVTR)

According to Peppas et al., 1987, the most difficultproblem in taking care of the burned victim was the factthat the victim may have lost most of their body liquid

due to evaporation and exudation. These will affect thedecrease of body temperature and accelerate the rate ofmetabolism. Therefore, the hydrogel wound dressing

must avoid or at least reduce the body liquid lost i.e. bycontrolling absorption and transmission as well as by

maintaining the high humidity in the wound area, inorder to accelerate the formation of granule andepitelesation process. Based on Table 1, it can be seenthat the WVTR values of PVA–PVP blended hydrogel

are around 80–200 g/m2/h. These values seem to be in anideal range for wound dressing. A higher value ofWVTR causes a faster drying of the wound. Though

there is not an exact ideal value of WVTR for wounddressing, the value must not be so high because it willcause a dry condition in the wound area. On the other

hand, if the WVTR value is so low, then it will make theaccumulation of exudates which may cause the decelera-tion of healing process and opens up the risk of bacterialgrowth. For comparison, Table 3 shows WVTR for

some commercial wound dressing values (Bruin et al.,

Table 1

The water content, water absorption and water vapor

transmission rate of different composition of PVA–PVP

blended hydogel.

PVP

conc. (%)

Composition

PVA : PVP

Water content

(EWC) (%)

Water abs.

(%) in 24 h

immersion

time

WVTR

(g/m2/h)

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

12 40:60 79.06 105 150.60

70:30 77.50 117 131.39

90:10 75.00 167 129.40

Fig. 3. Relationship between water absorption (%) and im-

mersion time (h) at different irradiation dose.

Table 2

The relationship between the water content and adhesiveness

PVP

concentration

% w/w

Water

content

(EWC) (%)

Adhesiveness

(gt)

2.4 89.5 6

3.6 88.2 7

4.8 87.1 9

6.0 85.6 10

7.2 74.7 12

M.T. Razzak et al. / Radiation Physics and Chemistry 62 (2001) 107–113110

1990). According to Bruin et al., 1990, an occlusivewound covering, such as Op Site (see Table 3) with a

WVTR of 33 g/m2/h, has a weakness point, i.e. it causesan accumulation of exudates under the covering and inturn causes infection.

3.5. Microbe penetration test

Based on the microbe penetration test, there were no

bacteria’s passing through the hydrogel during day byday observation for 14 days. Since no bacteria wasfound on the TSA medium, the PVA–PVP blended

hydrogel could be considered as a good barrier againstthe microbes. This characteristic is very important forhydrogel dressing, especially in protecting the wound

from further infection so that it may accelerate thehealing of wound.

3.6. In vitro assessment

The macroscopic observations of the wound healingeffect in terms of comfortability and the excudate

absorption performance of the hydrogel sample ascompared to Sofratulle and Sterilized Gauze were done.It was found that the PVA–PVP blended hydrogel and

Sofratulle have a better comfortability than that of thesterilized gauze when dressing are removed from thewound. The hydrogel adhered slightly to the wound and

caused only a little hemorphagic. The capability ofthe PVA–PVP blended hydrogel in absorbing woundexudates was observed as high as the Sterilized Gauze,

while Sofratulle nearly did not absorb any exudates.Furthermore the PVA–PVP blended hydrogel was betterin preventing the wound from contamination comparedwith the sterilized gauze and sofratulle. This is possible

because it has a good comfortability which are enable tocover the wound perfectly. It can be seen in Fig. 4, thatthe healing process which are reflected by the reduction

of the wound surface area seems to be proceeded quitefast up to 10 days, then it will be slowly until the woundwas fully recovered at the day of 18. There were no

significant difference on the time of complete recoveringof the wound. However the surface of recovered wound

treated with PVA–PVP blended hydrogel or sofratullewere observed smoother than that of treated withsterilized gauze.

Histological study was done by microscopical ob-servation of the wound healing process. Microscopicalobservation 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 woundsurface (see Fig. 5). The wound surface was covered byexudates layer which was consisted of the mixture of the

fibrin, tissue debris and polymorpho nuclear cell (PMN).The tissue bond underwent oidema (macrophage) andblood vessel look hyperemis. Besides that, the initial

granulation started to be formed. There were no bacteriaof fungi colonies found. At day 7, all wounds eithertested with PVA/PVP blended hydrogel, sofratulle or

sterilized gauze showed a significant inflammatoryreaction.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 PMAexudates (see Fig. 6). The epidermis did not yet containhair follicle and sebaceous gland, and the edge of the

wound became thicker due to proliferation of the epitelcells. These macroscopic and microscopic observationunder in vitro assessment revels that the PVA–PVP

blended hydrogel can meet the efficacy requirement andits healing rate was comparable to that Sterile Gauzeand Sofratulle. The hydrogel was also pleasant fell,comfortable, and does not disturb the formation of cells

and new tissue on the skin.

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

Fig. 4. Relationship between the mean surface area of the

wound.

M.T. Razzak et al. / Radiation Physics and Chemistry 62 (2001) 107–113 111

4. Conclusion

The PVA–PVP blended hydrogel shows some proper-ties which can meet the requirements of an ideal wound

dressing. For example, its absorb effectively the fluid,

pleasant in touch and painless in removal, exhibit highelasticity but also good mechanical strength, goodtransparency and can act as a barrier against themicrobes. This hydrogel wound dressing is highly

potential to be used in tropical environment.

Fig. 5. Histology of wound after 3 days of treatment with PVA–PVP blended hydrogel: (a) the wound covered by fibrin, debris and

PMN exudate, (b) hair follicles undergo degeneration and integration. Magnification: 40� .

Fig. 6. Histology of wound after 14 days of treatment with PVA–PVP blended hydrogel. Epidermis layer undergoes proliferation (a)

and information of dermis tissue bond which is consisted of PMN, eosinofil and macrophage (b). Magnification: 40� .

M.T. Razzak et al. / Radiation Physics and Chemistry 62 (2001) 107–113112

Acknowledgements

The author wish to thank Prof. Dr. J.M. Rosiak andDr. Nazly Hilmy, PhD, for their valuable suggestion.The authors also would like appreciate Dr. Iwan

Budiarso for his valuable discussion for in vitroassessment. 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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