Polymer International Polym Int 55:513–519 (2006)

Synthesis and characterizationof pH- and temperature-sensitive silksericin/poly(N-isopropylacrylamide)interpenetrating polymer networksWen Wu,1 Wenjing Li,2 Li Qun Wang,1∗ Kehua Tu1 and Weilin Sun1

1Institute of Polymer Science, Zhejiang University, Hangzhou 310027, China2Ningbo Institute of Technology, Zhejiang University, Ningbo 315100, China

Abstract: Interpenetrating polymer networks (IPNs) composed of silk sericin (SS) and poly(N-isopropylacryl-amide) (PNIPAAm) were prepared simultaneously. The properties of the resultant IPN hydrogels werecharacterized by differential scanning calorimetry and SEM as well as their swelling behavior at varioustemperatures and pH values. The single glass transition temperature (Tg) presented in the IPN thermogramsindicated that SS and PNIPAAm form a miscible pair. The swollen morphology of the IPNs observed by SEMdemonstrated that water channels (pores present in SEM micrographs) were distributed homogeneously throughout the network membranes. The swelling ratio of the IPNs depended significantly on the composition, temperatureand pH of the buffer solutions. The dynamic transport of water into the IPN membrane was analyzed based on theFickian equation. 2006 Society of Chemical Industry

Keywords: silk sericin; poly(N-isopropylacrylamide); interpenetrating polymer network; hydrogel

INTRODUCTIONInterpenetrating polymer networks (IPN) are three-dimensional networks formed from homogeneous orheterogeneous polymers crosslinked in the presenceof another one. Since there is no chemical bondingbetween the two component networks, each networkretains its own properties while the proportion of eachnetwork can be varied independently. In recent years,work has been done to combine the pH and tempera-ture sensitivity by forming IPN hydrogels.1–3 Amongthose, a poly(N-isopropylacrylamide) (PNIPAAm) gelis frequently chosen as one network for exhibiting adrastic swelling transition at its lower critical solutiontemperature (LCST) in aqueous solution, and theformed hydrogels have been evaluated as matrices fordrug delivery.4–11 In some of its applications, a limi-tation of PNIPAAm hydrogel is its intrinsically poormechanical properties and lack of sustained releasecapability.12–14 The incorporation of crosslinked PNI-PAAm into interpenetrating polymer networks hasbeen considered as a method of improving mechanicalproperties and sustained drug release over a longerperiod.

Silk sericin (SS) is one of the natural macromolec-ular proteins derived from silkworm which have beendiscarded during silk processing. Sericin is a water-soluble globular protein made of 18 amino acids,most of which have strongly polar side groups such ashydroxyl, carboxyl and amino groups.15,16 A numberof studies have been carried out in order to recover the

sericin for other uses. Lower-molecular-weight sericinpeptides or sericin hydrolysates are used in cosmet-ics, and high-molecular-weight sericin is mostly usedin biomedical materials, degradable biomaterials andfunctional biomembranes. Pure sericin is not easilyturned into membranes; however, it can be readilycrosslinked, co-polymerized, or blended with othermacromolecular materials.17–19 Up to now, biocom-patible sericin with numerous biological and pharma-cological applications has not been investigated as apotential drug carrier.

In this paper, we suggest the construction ofan IPN structure containing SS and PNIPAAm inorder to combine the differences of solubility ofSS in and out of its isoelectric point (PI) withthe thermosensitive properties of PNIPAAm. Theresultant IPN hydrogels may be both temperature- andpH-sensitive biomaterials. The swelling properties,LCSTs and miscibility of IPN hydrogels have beeninvestigated and reported here.

EXPERIMENTALMaterialsSS powder was a gift sample from WuXi Smiss Tech-nology Co. Ltd; N-isopropylacrylamide (NIPAAm)from Tokyo Chemical Industry Co. Ltd was puri-fied by recrystallization in toluene/petroleum ether

∗ Correspondence to: Li Qun Wang, Institute of Polymer Science, Zhejiang University, Hangzhou 310027, ChinaE-mail: lqwang@zju.edu.cn(Received 12 August 2005; revised version received 15 November 2005; accepted 28 November 2005)DOI: 10.1002/pi.1993

2006 Society of Chemical Industry. Polym Int 0959–8103/2006/$30.00

W Wu et al.

and dried under vacuum at room temperature; N,N ′-methylenebisacrylamide (MBAAm), ammonium per-oxydisulfate (APS), N,N,N ′,N ′-tetramethylethylene-diamine (TMEDA) and glutaraldehyde (25 wt%solution in water) (GA) were obtained in analyticalgrade and used without further purification.

Preparation of SS/PNIPAAm IPN hydrogelsSS/PNIPAAm hydrogels were prepared by the so-called simultaneous IPN method.20 SS and NIPAAmmonomer were dissolved in deionized water inpredetermined feed ratios at a total concentration of20 wt%. The weight ratios of SS to NIPAAm in themixture were set at 30:70, 40:60, 50:50, 60:40 and70:30, denoted as IPN-37, IPN-46, IPN-55, IPN-64 and IPN-73, respectively. The feed compositionsand sample identification of the reactions are listed inTable 1.

The mixtures of SS and NIPAAm were firststirred for 30 min under nitrogen atmosphere forhomogenization and to increase the entanglementdensity. Then the crosslinking agents, GA (5 wt%SS) and MBAAm (3 mol% NIPAAm) for SS andNIPAAm, and TMEDA (1 wt% NIPAAm) and APS(1 wt% NIPAAm) as an accelerator and initiator wereadded to the mixtures and vigorously stirred for about1 min. The mixtures were then poured into a sealedglass mold and reacted at 25 ◦C for 24 h under nitrogenatmosphere. The half-transparent films obtained werethoroughly immersed in deionized water at roomtemperature for five days in order to remove thereagent residues. The water was refreshed every 4 hduring this treatment. The IPN hydrogels were thencarefully cut into small disks (15 mm in diameterand 3 mm in thickness) and dried to constant weightunder vacuum. Homo-PNIPAAm and SS hydrogelswere prepared with the same procedure, and aredenominated Homo-N and Homo-S hereafter.

LCST of the IPN hydrogelsThe LCST behavior of the hydrogel samples wasdetermined using a Perkin Elmer Pyris1 DSC. Allhydrogel samples were immersed in deionized water atroom temperature and allowed to swell to equilibriumbefore DSC measurement. For each measurement,about 15 mg of equilibrium swollen sample (alongwith its water) was placed inside a hermetic aluminum

Table 1. Feed compositions of SS/PNIPAAm IPN hydrogels

Sample ID

CompositionHomo-

NIPN-37

IPN-46

IPN-55

IPN-64

IPN-73

Homo-S

SS (g) 0 0.6 0.8 1.0 1.2 1.4 2.0GA (mL) 0 0.6 0.8 1.0 1.2 1.4 2.0NIPAAm (g) 2.0 1.4 1.2 1.0 0.8 0.6 0MBAAm (mg) 81.8 57.2 49.0 40.8 32.7 24.5 0TMEDA (µL) 26.0 18.0 15.4 12.8 10.2 7.6 0APS (mg) 20.0 14.0 12.0 10.0 8.0 6.0 0

pan, then sealed tightly with a hermetic aluminumlid. The thermal analysis was performed from −20 to70 ◦C on the swollen hydrogel samples at a heatingrate of 10 ◦C min−1 under dry nitrogen (flow rate of20 mL min−1). The onset point of the endothermalpeak was used to determine LCST.

Glass transition temperature of the IPNhydrogelsThe glass transition temperatures (Tg) of driedhydrogels were investigated by Perkin Elmer Pyris1DSC. For each DSC measurement, about 10 mg ofdry hydrogel was placed inside a hermetic aluminumpan and sealed tightly with a hermitic aluminum lid.First, the sample was heated from 50 to 180 ◦C ata heating rate of 10 ◦C min−1 to remove its thermalhistory. Then it was reheated from 50 to 180 ◦C ata heating rate of 10 ◦C min−1. The glass transitionwas determined from the trace of this second run,as the intersecting point of two tangent lines fromthe baseline and the slope of the endothermic peak,according to standard Tg measurements and criterionof Tg at �Cp/2.

Morphology of the IPN hydrogelsCryofixation was used to prepare the swollen hydrogelsfor SEM. The hydrogel samples were first equilibratedin deionized water at room temperature for 24 h, thenquickly frozen in liquid nitrogen, and freeze-dried ina freeze drier (LGJ-10, China) until all of the watercontained in the samples was sublimed. The frozendried samples were carefully fractured and mountedonto aluminum studs and sputter-coated with goldfor 240 s. The interior morphology was investigatedusing a scanning electron microscope (XL 30ESEM,Philips).

Swelling experiments of the IPN hydrogelsPre-weighed dried disk-shaped samples were immer-sed in deionized water in the temperature range25–45 ◦C, which covers the expected LCST rangeof the hydrogels. After a predetermined time, thehydrogels were removed from the water bath andblotted with filter paper to remove excess water onthe surface and weighed at each time interval untilthey reached equilibrium. The average value of threemeasurements was taken for each sample. The swellingratio can be calculated as a function of time:

Swelling ratio (%) = [(Ws − Wd)/Wd] × 100 (1)

where Ws and Wd are the weight of the swollen anddry state of the sample, respectively.

Samples for pH dependence experiments weremeasured as above, at 15 and 37 ◦C in buffer solutionswhere pH values ranged from 2 to 11, which includesthe PI of SS.

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Silk sericin/poly(N-isopropylacrylamide) interpenetrating polymer networks

RESULTS AND DISCUSSIONLCST of IPN hydrogelsA suitable method for detecting the phase transitiontemperature in aqueous polymer solutions is differen-tial scanning calorimetry (DSC).21 The DSC data ofIPNs shown in Fig. 1 demonstrate that the LCST ofthe IPNs is almost the same as that of the Homo-N atca 33.5 ◦C. This suggests that the LCST behavior iscaused by a critical hydrophobic/hydrophilic balanceof the isopropyl groups and amide groups of the PNI-PAAm. The ratios of hydrophobicity/hydrophilicity ofPNIPAAm as a whole are a main determinant of theirLCST, namely that the sericin concentration showsan insignificant impact on the LCST of the IPNs.

Miscibility of IPN hydrogelsFigure 2 shows the DSC thermograms of the IPNhydrogels. Contrasting with the glass transitiontemperature of homoPNIPAAm at 139.8 ◦C and thatof homoSS at 161.1 ◦C,22–24 a single Tg appears inall of the IPN samples, ranging from 140 to 160 ◦C,indicating that SS and PNIPAAm components forma miscible pair. The Tg values of the IPNs movegradually to higher temperatures with the increase of

25 30 35 40 45

33.5°C

IPN-73

IPN-64

IPN-55

IPN-46

IPN-37

Homo-N

Temperature(°C)

Hea

t Flo

w (

End

othe

m u

p)

Figure 1. DSC thermograms of swollen SS/PNIPAAm IPNs.

80 100 120 140 160

Homo-S

161.1°C

152.3°C

151.7°C

150.7°C

147.9°C

145.9°C

139.8°C

IPN-73

IPN-64

IPN-55

IPN-46

IPN-37

Homo-N

Temperature(°C)

Hea

t Flo

w (

End

othe

m u

p)

Figure 2. DSC thermograms of dried SS/PNIPAAm IPNs.

SS content in the INPs. The strong intermolecularinteractions between SS and PNIPAAm are supposedto play an important role in the resulting miscibilityof the two components. Fourier transform infraredspectroscopy (FTIR) has been widely used todetect the molecular interactions in polymer blendsystems.25–30 FTIR spectra of SS, PNIPAAm andtheir blend are shown in Fig. 3. In contrast to theAmide I band of PNIPAAm centered at 1643 cm−1

and that of SS at 1659 cm−1, the Amide I band ofthe 50:50 w/w blend of PNIPAAm and SS centers at1652 cm−1 with an apparent downward wavenumbershoulder. Amide II band mainly from δNH appearsat 1537 cm−1 and is also present with a significantshoulder at 1515.6 cm−1. The shoulder peaks of thesebands appearing at lower wavenumbers are all signs ofthe formation of hydrogen-bonding between SS andPNIPAAm chains,31 which is believed to be the drivingforce for the miscibility of PNIPAAm/SS IPNs.

The interior morphology of all the swollen samplesexhibits a highly porous honeycomb-like structureas shown in Fig. 4. As discussed above, dueto the miscibility between SS and PNIPAAm,

1700 1650 1600

interaction area

Abs

orba

nce

SSPNIPAAmSS+PNIPAAm

1550 1500

SSPNIPAAmSS+PNIPAAm

interaction area

Abs

orba

nce

Wavenumber (cm-1)

Wavenumber (cm-1)

Figure 3. FTIR spectra of SS, PNIPAAm and SS/PNIPAAm blend inthe acrylamino and amino band regions.

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Figure 4. SEM micrographs of swollen IPN membranes.

the pores are basically distributed homogeneouslythroughout the IPN membranes, though generally themorphology of IPNs depends mainly on the gelationand phase separation of the two polymers duringthe polymerization and cross-linking process.32 Thethickness of the pore walls of the samples is about3 µm. The sizes of the pores tend to decrease with theincrease of SS content.

Swelling behavior of the IPN hydrogelsEffect of temperatureThe time-dependent swelling behavior of IPN hydro-gels in deionized water at 25, 37 and 45 ◦C is shown inFig. 5. It is observed that both hydrogel componentsswell rapidly and reach an equilibrium state within6 h. The swelling behavior of Homo-S is only slightlyaffected by the temperature. In contrast, IPNs exhibit

significant temperature-dependent swelling profiles.At 25 and 37 ◦C, below and near its LCST, IPN-37shows the highest swelling ratio as a time-dependentswelling behavior, while IPN-73 exhibits the lowest.As expected, at 45 ◦C, that is, above the LCST ofthe hydrogels, the trend is reversed. It is believedthat when the temperature is below the LCST PNI-PAAm is more hydrophilic than SS, which results inan increased swelling ratio of the IPNs with increasingmolar ratio of the hydrophilic groups of PNIPAAm inIPNs, while at temperatures above the LCST PNI-PAAm tends to become more hydrophobic, whichreverses the swelling profile of the IPNs.

The temperature-dependent swelling behaviorshown in Fig. 6 shows that all of the IPN sam-ples possess a similar swelling profile, and thatthe swelling ratio decreases dramatically as the

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Silk sericin/poly(N-isopropylacrylamide) interpenetrating polymer networks

0 50 100 150 200 250 3000

200

400

600

800

1000

Swel

ling

ratio

(%)

Time(min)

IPN-37 25°C

IPN-55 25°C

IPN-73 25°C

IPN-37 37°C

IPN-55 37°C

IPN-73 37°C

IPN-37 45°C

IPN-55 45°C

IPN-73 45°C

Figure 5. Time-dependent swelling ratio of IPN hydrogels in deionized water at 25, 37 and 45 ◦C.

25 30 35 40 450

200

400

600

800

1000

Swel

ling

ratio

(%)

Temperature(°C)

IPN-37IPN-55IPN-73

Figure 6. Swelling ratio of IPN hydrogels after reaching equilibrium inwater as a function of temperature.

temperature increases toward LCST. The equilib-rium swelling ratios of IPN-37 decrease from 973%to 371% with the temperature elevated from 25 to37 ◦C, in comparison to IPN-55, which changes from603% to 335% and IPN-73 from 403% to 279%. Ata temperature of 45 ◦C the swelling levels of the sam-ples become closer, and the differences are believed torelate to the composition of the IPNs. At this stage,the content of SS in the IPNs is the determinant factorfor hydration of the INPs.

Effect of pHSS is a weak amphipathic polyelectrolyte based on its18% acidic and 8% basic residues, which makes itsensitive to pH. The pH-dependent swelling behaviorof the IPNs at temperatures of 15 and 37 ◦C are shownin Fig. 7, where the pH of the buffer solutions changesin the range 2–11. Homo-S and Homo-N are plottedfor comparative purposes. Within the investigated pH

range, all the IPN hydrogels show similar trends.Homo-N shows a temperature-sensitive characteristic.Its swelling ratio is much lower at 37 ◦C than at 15 ◦C,and at pH 7.5, Homo-N shows a relatively lowerswelling ratio due to the increase of ionic strength inthe buffer solution, which is recognized as a salting-out effect.33,34 The swelling ratio of Homo-S increasesa little with the elevation of temperature, and showsa minimum at about pH 4.4 because the SS sidechains are almost in their non-charged, hydrophobicform. Decreasing the pH of the buffer solutions below4.4 (SS is protonated) or increasing it above 4.4(SS is charged) results in increased swelling ratios ofHomo-S. As can be seen, regardless of the compositionof the hydrogels all the samples swell less at pH 4.4and pH 7.5, but have a higher swelling ratio in acidicor basic conditions. At 15 ◦C, below the LCST, theswelling ratios increase in the order IPN-37 > IPN-46> IPN-55 > IPN-64 > IPN-73, whereas the order iscompletely reversed at 37 ◦C, above the LCST of theIPNs. This also indicates that the equilibrium swellingratio is significantly affected by the composition of theIPNs, and therefore the swelling profile of the IPN canbe readily modulated by changing the feed ratio whenpreparing the IPN. The IPNs composed of SS andPNIPAAm show simultaneous pH and temperaturesensitivity.

Swelling kinetics of the IPN hydrogelsThe swelling kinetics of a hydrogel depend onthe mode of diffusion of water molecules into thehydrogel matrix and the subsequent relaxation ofits macromolecular chains. In order to obtain aninsight into the mechanism of the swelling process ofPNIPAAm/SS IPNs, the following equation is used:35

Mt/M∞ = ktn (2)

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2 6 8 10

200

300

400

500

600

700

800

900

1000

1100

1200

Swel

ling

ratio

(%)

Swel

ling

ratio

(%)

pH

15°CHomo-SIPN-37IPN-46IPN-55IPN-64IPN-73Homo-N

50

100

150

200

250

300

350

400

450

500

550

600

650

4

2 6 8 10pH

4

37°CHomo-SIPN-37IPN-46IPN-55IPN-64IPN-73Homo-N

Figure 7. Swelling ratio of IPN hydrogels in buffer solutions at 15 and 37 ◦C as a function of pH and hydrogel composition.

where Mt and M∞ represent the amount of wateruptake at time t and at equilibrium time, respectively,k is a characteristic constant of the hydrogel and n is acharacteristic exponent of the mode penetration. Thevalue n is used in the determination of the mechanismof swelling kinetics. For n = 0.5, corresponding to aFickian transport, the rate of diffusion is much lowerthan the rate of relaxation; for n = 1, the diffusion isvery fast, contrary to the rate of relaxation; and for0.5 < n < 1, the solute transport will be anomalous.Calculation of the exponent n is achieved by plottingthe data in log-log plots according to Eqn (3) and bylinear regression to determine the slope:

ln(Mt/M..) = ln k + n ln t (3)

Figure 8 shows the water uptake of the IPN hydro-gels at 25, 37 and 45 ◦C, respectively, according toEqn (3). The n values of the different gel composi-tions as a function of temperature are given in Table 2.

At temperatures below LCST (25 ◦C), the hydrogelshave an average n value of about 0.57, suggesting thatthe rate of water diffusion is relatively lower than thatof macromolecular relaxation. This result may show,on the other hand, the existence of strong intermolec-ular interactions between PNIPAAm and SS. Whenthe temperature is elevated close to and above theLCST (37 and 45 ◦C), the hydrogels register a greatdecrease in n value. It is believed that this reflects theincreased resistance tendency of the collapsed PNI-PAAm moiety to the advancing water molecules. Thetransport of water molecules into the hydrogel matrixis significantly blocked.

CONCLUSIONSIn this study, IPN hydrogels based on SS and PNI-PAAm were prepared by the so-called simultane-ous IPN method using GA and MBAAm as theircrosslinking agent, respectively.

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1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5

-2.0

-1.5

-1.0

-0.5

0.0

IPN-37 25 °C

IPN-55 25 °C

IPN-73 25 °C

ln(M

t/M∝

)

ln t

IPN-37 37°C

IPN-55 37°C

IPN-73 37°CIPN-37 45°C

IPN-55 45°C

IPN-73 45°C

Figure 8. Plot of ln(Mt/M∞) against ln t for IPN hydrogels.

Table 2. n values for the IPN hydrogels at various temperatures

n value for

Temperature (◦C) IPN-37 IPN-55 IPN-73

25 0.55 0.63 0.5637 0.46 0.44 0.3545 0.26 0.27 0.25

Thermal data reveal that LCST depends mainly onthe PNIPAAm moiety. Only a single Tg is observed foreach IPN sample, indicating that SS and PNIPAAmform a miscible pair. The intermolecular interactionsbetween PNIPAAm and SS, revealed by FTIR spec-troscopy, are believed to be the main driving forcefor the miscibility of the two components. The mor-phology of the swollen IPNs exhibits a relativelyhomogeneous pore distribution throughout the IPNmembranes.

The swelling ratios of the IPN hydrogels are signifi-cantly affected by the temperature and pH values of thebuffer solution. The swelling ratio decreased dramat-ically as the temperature increased toward the LCSTof the IPNs. The equilibrium swelling ratios, whichare strongly composition-dependent, exhibit low val-ues at pH 4.4 and 7.5 because of the PI of SS and thesalting-out effect.

The swelling kinetics of the IPN hydrogels exhibitopposite trends at temperatures below and abovethe LCST of the INP hydrogels, mainly because ofthe hydrophilic–hydrophobic transformation of thePNIPAAm component.

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