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Radiation Physics and Chemistry 76 (2007) 1342–1346

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Controlling of pore size and distribution of PDMAEMA hydrogelsprepared by gamma rays

Murat S-ena,�, Osman Agus-a, Agnes Safranyb

aDepartment of Chemistry, Polymer Chemistry Division, Hacettepe University, 06532 Beytepe, Ankara, TurkeybInstitute of Isotopes, Hungarian Academy of Sciences, H-1121 Budapest XII, Konkoly Thege Miklos ut 29-33, P.O.B. 77, H-1525 Budapest, Hungary

Abstract

In this study, radiation synthesis and controlling of pore size and distribution of poly(N, N-dimethylaminoethyl methacrylate)

(PDMAEMA) hydrogels have been investigated. Monomer mixtures containing various compositions of DMAEMA, water and ethylene

glycol dimethacrylate (EGDMA) and poly(ethylene glycol) (PEG) have been prepared and irradiated. The molecular weight between

cross-links of P(DMAEMA) hydrogels prepared in the presence of PEG increased with increasing amount of PEG in the initial mixture

from 1% to 20%. Hydrogels with highest mesh size were obtained by using 20% PEG10 000. Upon PEG addition, an increase in the

equilibrium degree of swelling (Q) was observed with increasing molecular weight of PEG until a molecular weight of 10 000. Maximum

swelling was reached for systems containing 1% and 5% PEG10 000. SEM micrographs showed homogeneous pore structure of the

hydrogels with open pores at lower pH.

r 2007 Elsevier Ltd. All rights reserved.

Keywords: Hydrogels; Dimethylaminoethyl methacrylate; Radiation; Cross-linking; Pore size

1. Introduction

The preparation of poly(N, N-dimethylaminoethyl metha-crylate) (PDMAEMA) and its copolymers has gainednoticeable interest and a series of papers were publishedby Siegel and Firestone in the late eighties (Firestone andSiegel, 1988; Siegel and Firestone, 1988). They investigatedthe influence of comonomer n-alkyl methacrylate (n-AMA)and methyl methacrylate (MMA) on the pH dependentswelling properties and swelling kinetics. It was found thatthe extent of the transition from the collapsed hydrophobicstate to the hydrophilic state changed depending on thecomonomer composition. Generally, increasing of theproportion of n-AMA to MMA decreased the extent ofthe transition and shifted it to lower pH. It was also observedthat longer n-AMA side chains also reduced the extent of thetransition.

ee front matter r 2007 Elsevier Ltd. All rights reserved.

dphyschem.2007.02.028

ing author. Tel.: +90312 2977989; fax +90 312 2977989,

3.

ess: msen@hacettepe.edu.tr (M. S-en).

In recent years much more attention has been directed toPDMAEMA hydrogels that undergo controllable volumechanges in response to small variations of pH andtemperature changes in solution condition for use in avariety of novel applications including controlled drugdelivery (Traitel et al., 2000; Hinrichs et al., 1999) and as agene transfer agent (Rungsardthong et al., 2001; Takedaet al., 2004).In our previous study, we proposed that a small amount

of ethylene glycol dimethacrylate (EGDMA) can facilitatethe cross-linking of DMAEMA effectively during lowdose rate gamma irradiation and improve the cross-linkefficiency approximately eightfold when only 0.05%concentration in the initial monomer mixtures was used(Uzun et al., 2003). We also reported that irradiation dose,comonomer VP and cross-linking agent EGDMA affectthe gelation percentage and network structure of DMAE-MA hydrogels. The effects of all these parameters on thepH and temperature response characteristics and enthalpyand entropy changes appearing in the w parameter for theP(DMAEMA-co-VP)–water system were also determinedin our previous study (S-en and Sarı, 2005).

ARTICLE IN PRESSM. S- en et al. / Radiation Physics and Chemistry 76 (2007) 1342–1346 1343

2. Experiments

For the preparation of PDMAEMA hydrogels (DMAE-

MAxPEGy) in the presence of poly ethylene glycol (PEG)5ml of DMAEMA was mixed with 1.5ml 1.0%, 5.0%,10.0%, 20.0% PEG solution and 0.05% by volumeEGDMA (volume EGDMA/volume DMAEMA) wasadded into these solutions. The molecular weight ofPEGs used as diluents in the polymerization medium were2000, 10 000 and 20 000 g/mol. In the gel name x and y

represent the % of PEG solution from which 1.5ml wasadded into the initial mixture and the molecular weight ofPEG as kD, respectively. Monomer solutions thus pre-pared were placed in PVC straws of 4mm diameterand irradiated up to 4.0 kGy in Gammacell-220 typeg-irradiator at a fixed dose rate of 0.16 kGy/h. Hydrogelsobtained in long cylindrical shapes were cut into pieces of324mm and stored.

Dried hydrogels were left to swell in various K2HPO4

and KH2PO4 phosphate buffer solutions at pH 3–8.Swollen gels were removed from the swelling medium atregular intervals, dried superficially with filter paper,weighed and placed back in the same medium. Themeasurements were continued until a constant weight wasreached for each sample. This weight was used to calculatethe volume fraction of polymer, n2m, and the equilibriumdegree of swelling (EDS), (Q), of the gel swollen toequilibrium in aqueous solution.

The mechanical properties were determined at roomtemperature by uniaxial compression experiments at acrosshead speed of 5mm/s until failure, using a Zwick Z010model Universal Testing Instrument and uniaxial compres-sion module, equipped with a 1 kN compression load cell.The mechanical properties of the hydrogels were measuredin their relaxed state (after preparation).

The pore structure of the gels was monitored by usingJeol JSM 5600 LV scanning electron microscope. For thesestudies the hydrogels were first swollen in pH 3 and pH 7buffer solutions, then lyophilized, and sputter coated withplatinum/palladium.

3. Results and discussion

3.1. Preparation of PDMAEMA hydrogels in the presence

of PEG

In order to increase the pore size of hydrogels weadded water soluble low molecular weight PEGS intothe initial mixtures. The molecular weight of PEGsused as diluents in the polymerization medium was2000, 10 000 and 20 000 g/mol. Percentage gelation i.e.percentage conversion of monomer (DMAEMA), cross-linking agent (EGDMA) into insoluble networks, wasbased on the total weight of these two monomers in theinitial mixture. % gelation of DMAEMA decreased from99% to 95% with decrease of molecular weight of PEG

and with increasing PEG content in the initial mixture(Agus-, 2005).After preparation of hydrogels, FTIR spectra were taken

(spectra not given in the text). Two characteristic peaks ofPEG at 1140 and 845 cm�1 were observed for non-washedDMAEMA20PEG20 hydrogel as a sharp and shoulderpeak, respectively. Both peaks disappeared from thespectra after washing, indicating that PEG can easily beremoved from the hydrogels.On the other hand, these two characteristic peaks of

PEG stayed in the FTIR spectra of washed DMAEMA5-PEG20, DMAEMA10PEG20 and DMAEMA20PEG20hydrogels indicating that PEG20 000 probably formedinter-penetrating network with DMAEMA monomer.The higher gelation percentage of hydrogels with PEG20 000 in the initial mixture when compared to mixturescontaining PEG2000 and PEG 10 000 was also attributedto this inter-penetrating network and/or grafted PEGmolecules.

3.2. Characterization of network structure of PDMAEMA-

PEG hydrogels

For the characterization of the network structureand determination of the molecular weight betweencross-links, Mc, of DMAEMA hydrogels, the swellingproperties at non-ionized state (pH 7) were first investi-gated. After swelling experiments the uniaxial compressionwas applied on the gels swollen at pH 7. During thedetermination of the shear modulus, the experiment wasstopped before the complete deformation of the hydrogelsystem, in order to obtain the initial deformation. Shearmodulus values were calculated by using the elasticdeformation theory and the following equation (Markand Erman, 1988):

f ¼ Gðl� l�2Þ. (1)

When the equation is applied to the initial stages ofdeformation, plots of f vs. ðl� l�2Þ yield straight lines. TheG value was calculated from the slope of the lines, andlisted in Table 1. Mc values were calculated by using Eq. (2)and shown in Table 1 (Okay and Durmaz, 2002).

G ¼r

Mc

RTn2=32r n1=32m , ð2Þ

x ¼ n1=32m Cn

2Mc

Mr

� �� �1=2l. ð3Þ

The mesh size of PDMAEMA hydrogels were calculatedby using Eq. (3) (Peppas and Mikos, 1986; Agus-, 2005)and plotted in Fig. 1. As seen from Fig. 1, additionof PEG during the preparation of DMAEMA hydrogelscaused a decrease in the cross-link density and an increasein the mesh size. The highest mesh size was reachedwith 20% of PEG10 000. The smaller pores of thehydrogels containing PEG20 000 was probably due tothe formation of inter-penetrating network structure, or

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20

25

30

35

40

45

DMAEMAXPEG2

DMAEMAXPEG10

DMAEMAXPEG20

Mes

h si

ze, n

m

PEG (%)0 5 10 15 20

Fig. 1. Effect of PEG content in the initial mixture on the mesh size of

PDMAEMA hydrogels.

0

20

40

60

80

100 pH3

pH4

pH5

pH6

pH7

pH8

Equ

ilibr

ium

Deg

ree

of S

wel

ling,

(Q)

PEG (%)0 5 10 15 20 25

Fig. 2. The effect of pH and the amount of PEG10 000 in the initial

mixture on the EDS values of PDMAEMA hydrogels.

Table 1

Structural properties of PDMAEMA hydrogels prepared in the presence of PEG

Q (%) r ðg=cm3Þ ðn2mÞ ðn2rÞ G (kPa) Mc (g/mol) x (nm)

P(DMAEMA)/EGDMA 903 1.055 0.095 0.764 17 63 482 22.95

DMAEMA1PEG2 1181 1.080 0.074 0.813 21 50 664 22.10

DMAEMA5PEG2 1301 1.057 0.067 0.808 13 77 460 28.15

DMAEMA10PEG2 1920 1.061 0.046 0.817 11 82 634 32.55

DMAEMA20PEG2 2563 1.052 0.037 0.829 9 94 633 37.19

DMAEMA1PEG10 1290 1.053 0.068 0.802 19 52 797 23.14

DMAEMA5PEG10 2370 1.059 0.038 0.787 10 83 770 34.71

DMAEMA10PEG10 2506 1.051 0.036 0.847 9 94 985 37.56

DMAEMA20PEG10 2507 1.053 0.036 0.874 8 109 097 40.26

DMAEMA1PEG20 1997 1.052 0.045 0.787 12 72 955 30.78

DMAEMA5PEG20 1350 1.053 0.064 0.792 18 54 315 23.90

DMAEMA10PEG20 1539 1.057 0.054 0.837 19 50 740 24.31

DMAEMA20PEG20 2452 1.053 0.043 0.863 9 101 510 36.81

M. S- en et al. / Radiation Physics and Chemistry 76 (2007) 1342–13461344

grafting. Increasing the amount of PEG20 000 in theinitial mixture resulted in an increase in the mesh sizebut this increase was not as sharp as for PEG2000and PEG10 000 (except DMAEMA20PEG20 hydrogelsystem).

3.3. Swelling of PDMAEMA hydrogels in buffer solutions

In order to follow the pH response of the PDMAEMAhydrogels prepared in the presence of PEG, dry samplesare allowed to swell to equilibrium in phosphate buffer atvarious pH, fixed ionic strength ðI ¼ 0:01Þ and temperatureð25 �CÞ. Fig. 2 shows the changes in the EDS ofDMAEMAxPEG10 hydrogels with the changing pHvalue. Consistent with poly-electrolytic systems, swellingof these gels are strongly dependent on pH (S-en and

Guven, 2001; S-en et al., 1999). A decrease in the pH from 8to 2 caused a significant increase in the equilibrium volumeswelling ratio of hydrogels. Among all PEG contentsmaximum extent of swelling was reached at pH 3, thisbeing due to the complete protonization of amine groups ofPDMAEMA at this pH value.In order to investigate the effect of molecular weight of

PEG on the swelling behavior of PDMAEMA hydrogels,the molecular weight of PEG was plotted versus EDS (Q).As seen from Fig. 3, Q increases with increasing molecularweight of PEG until 10 000 molecular weight. Addition ofPEG with a molecular weight over 10 000 caused a slightdecrease of the EDS. When 1% and 5% PEG was used inthe initial mixture, the maximum extent of swellingwas obtained with PEG10 000 (Agus-, 2005). However,for the hydrogels containing 10% and over 10% PEGmaximum swelling was reached at a molecular weight of2000 (Agus-, 2005).

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Fig. 5. SEM pictures of: (a) DMAEMA1PEG2; (b) DMAEMA5PEG2; (c) DM

7. The magnification is 200�.

20

24

28

32

36

40

44

48

52

pH3

pH4

pH5

pH6

pH7

pH8

Mes

h si

ze, (

nm)

Molecular weight of PEG (g/mol)

5000 10000 15000 20000 250000

Fig. 4. Dependence of the mesh size of PDMAEMA hydrogels on the pH

of the swelling solution and the molecular weight of PEG. The amount of

PEG in the initial mixture is 5%.

10

20

30

40

50

60

70

80

90

100

pH3

pH4

pH5

pH6

pH7

pH8

Equ

ilibr

ium

Deg

ree

of S

wel

ling,

(Q)

Molecular weigh t of PEG5000 10000 15000 20000 250000

Fig. 3. Dependence of the EDS of PDMAEMA hydrogels on the pH of

the swelling solution and the molecular weight of PEG. The amount of

PEG in the initial mixture is 5%.

M. S- en et al. / Radiation Physics and Chemistry 76 (2007) 1342–1346 1345

In order to investigate the effect of pH on the meshsize, the mesh size values (x) of hydrogels were calculatedby using Eq. (3) and given in Fig. 4. The mesh sizeincreased approximately twofold for all PDMAEMAhydrogels.

3.4. SEM studies

The effect of pH and the amount of PEG2000 on thepore structure of hydrogels were monitored by using ascanning electron microscope. In Fig. 5, SEM pictures ofhydrogels swollen in pH 3 are shown. The pore structure ishomogeneous and the pores are open at this pH, asexpected. The pictures also show that increase of PEG2000content in the initial mixture increased the pore size of thehydrogel.

4. Conclusion

The aim of this study was to regulate the mesh sizeof DMAEMA hydrogels with various additives inthe initial mixture. For this aim, hydrogels have beenprepared by changing the percentage and the molecularweight of added PEG in the initial mixture. The meshsize of PDMAEMA hydrogel is 22.9 nm when only0.05% EGDMA is used. The mesh size decreased to6.4 nm with increasing content of cross-linking agent(EGDMA) from 0.05% to 1.0% (S-en and Sarı, 2005).However, upon the addition of PEG2000 and PEG10 000in the initial mixture the mesh size has increasedapproximately twofold.

AEMA10PEG2; (d) DMAEMA20PEG2 hydrogel systems swollen at pH

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