Arabian Journal of Chemistry (2013) xxx, xxx–xxx

King Saud University

Arabian Journal of Chemistry

www.ksu.edu.sawww.sciencedirect.com

ORIGINAL ARTICLE

Stability of poly(N-isopropylacrylamide-co-acrylic

acid) polymer microgels under various conditions

of temperature, pH and salt concentration

Zahoor H. Farooqib, Hafeez Ullah Khan

a, Syed Mujtaba Shah

a,

Mohammad Siddiq a,*

a Department of Chemistry, Quaid-I-Azam University, Islamabad 45320, Pakistanb Institute of Chemistry, University of the Punjab, New Campus Lahore 54590, Pakistan

Received 16 January 2013; accepted 20 July 2013

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KEYWORDS

Microgels;

pH sensitivity;

Stability;

Temperature sensitivity

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Abstract This research article describes the colloidal stability of poly(N-isopropylacrylamide-co-

acrylic acid) [P(NIPAM-co-AAc)] polymer microgels with different acrylic acid contents in aqueous

medium under various conditions of temperature, pH and sodium chloride concentrations. Three

samples of multi-responsive P(NIPAM-co-AAc) polymer microgels were synthesized using different

amounts of acrylic acid by free radical emulsion polymerization. Dynamic laser light scattering was

used to investigate the responsive behavior and stability of the prepared microgels under various

conditions of pH, temperature and ionic strength. The microgels were found to be stable at all

pH values above the pKa value of acrylic acid moiety in the temperature range from 15 to 60 �Cin the presence and absence of sodium chloride. Increase in temperature, salt concentration and

decrease in pH causes aggregation and decreases the stability of microgels due to the decrease in

hydrophilicity.ª 2013 Production and hosting by Elsevier B.V. on behalf of King Saud University.

1. Introduction

Microgels have rapidly gained importance in field of materials

science owing to their potential applications in drug delivery

90642147.

(M. Siddiq).

Saud University.

g by Elsevier

ng by Elsevier B.V. on behalf of K

7.031

qi, Z.H. et al., Stability of poly(N-concentration. Arabian Journal of

(Murthy et al., 2003), pollution control (Morris et al., 1997), en-hanced oil recovery (Sun et al., 2011), sensors (Retama et al.,

2003), catalysis (Lee et al., 2008), fabrication of photoniccrystals (Jones and Lyon, 2000), template-based synthesis ofinorganic nanoparticles (Zhang et al., 2004) and chemical

separation (Nilsson and Hansson, 2005). A large number ofapplications of microgels arises from their ability to undergoreversible volume phase transitions in response to externalstimuli such as a change in pH (Nisato et al., 1999), temperature

(Dowding et al., 2000) and ionic strength of the surroundingmedium (Lopez-Leon et al., 2007). Poly(N-isopropylacrylam-ide) [P(NIPAM)] is a widely studied temperature responsive

ing Saud University.

isopropylacrylamide-co-acrylic acid) polymer microgels under variousChemistry (2013), http://dx.doi.org/10.1016/j.arabjc.2013.07.031

2 Z.H. Farooqi et al.

polymer microgel (Jones and Lyon, 2000). From applicationpoint of view, microgels would be much favorable if they couldrespond to several stimuli simultaneously. Therefore N-isopro-

pylacrylamide (NIPAM) is copolymerized with ionic mono-mers to get multiresponsive microgels. For examplecopolymerization of NIPAM with ionic monomer containing

carboxylic acid groups form a pH sensitive microgel in additionto the temperature responsive particles. The combination of ac-rylic acid (AAc) (Naeem et al., 2012) and NIPAM is largely

used to prepare pH responsive polymer microgels, becauseAAc is hydrophilic and can increase the volume phase transi-tion temperature (VPTT). Microgels with tunable VPTT havea potential to be used for biomedical applications (Farooqi

et al., 2011a,b). They assigned a photoresponsive drug deliverysystem based upon gold (Au) nanorods and P(NIPAM-co-AAc) hybrid material (Gorelikov et al., 2004). Jones and his

coworkers prepared poly(N-isopropylacrylamide-co-acrylicacid) [P(NIPAM-co-AAc)] core–shell microgel and studied itsfunctioning for physiological applications. They studied its

working at pH 3.5 and 6.5 under 0–0.8 M saline solutions(Jones and Lyon, 2003). Kim also synthesized microspheresof NIPAM and AAc and investigated its thermosensitivity

within 25–48 �C range at pH 3.0 and 6.5 (Kim et al., 2004). Theysynthesized P(NIPAM-co-AAc) microgels and investigatedtheir pH and temperature responsive bahaviour in aqueousmedium (Debord and Lyon, 2003). Zhang et al. designed a glu-

cose sensor by the chemical reaction of P(NIPAM-co-AAc)microgels with phenylboronic acid in the presence of N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride

(EDC) catalyst (Zhang et al., 2006). Mohan et al. used P(NI-PAM-co-AAc) microgels as microreactor to synthesize Agnanoparticles. They were able to tune optical properties of

nanoparticles by the variation of pH and temperature of thesurrounding medium (Mohan et al., 2010).

It is important to investigate the range of stability of P(NI-

PAM-co-AAc) microgels under various conditions of temper-ature, pH and salt concentrations for all the aboveapplications. To the best of our knowledge, no one has re-ported stability of P(NIPAM-co-AAc) microgels under such

conditions in a systematic way in the previous studies.Herein we prepared P(NIPAM-co-AAc) microgels with dif-

ferent feeding contents of AAc and NIPAM, and investigated

their responsive behavior in the presence of various stimuli likepH, temperature and NaCl concentration using DynamicLight Scattering (DLS). We reported the stability of microgels

under various conditions and determined the range of temper-ature, pH and ionic strength in which microgel is stable. Theaggregation behavior of the microgels has been explained onthe basis of proposed theories.

2. Experimental

2.1. Materials

NIPAM and AAc were purchased from Sigma–Aldrich while

N,N-methylenebis(acrylamide) (BIS) was obtained from AC-ROS. NIPAM was purified by recrystallization from n-hexaneand dried in an oven, prior to use. AAc was purified by distil-

lation under reduced pressure. Ammonium persulfate (APS),sodium dodecylsulfate (SDS) and BIS were used as received.Water used for all reactions, solutions preparation and polymer

Please cite this article in press as: Farooqi, Z.H. et al., Stability of poly(N-conditions of temperature, pH and salt concentration. Arabian Journal o

purification was distilled and deionized. The pH values weremeasured on a WTW Inolab pH 720 pH meter.

2.2. Synthesis of P(NIPAM-co-AAc) microgels

For synthesis of sample G1, 0.01237 mol of NIPAM,0.000214 mol of BIS, 0.000197 mol of SDS and 0.000721 mol

of AAc were dissolved in 100 mL of deionized water in a threenecked round bottom flask which was equipped with a con-denser and nitrogen inlet. The reaction mixture was heated

at 70 �C under a gentle stream of nitrogen. After 1 h, polymer-ization was started with the addition of 5 mL APS solution(0.06 M). The resulting microgels were purified by dialysis

for 1–2 weeks using Spectra/Por molecular porous membranetubing (cutoff 12,000–14,000) against very frequently changedwater at room temperature, and followed by centrifugation.Samples G2 and G3 were prepared and purified using the same

method. The compositions of all the microgel samples are gi-ven in the Table 1.

2.3. Characterization

DLS was used to investigate the responsive behavior of micro-gels. Before taking measurement, all the solutions of microgel

were filtered through a Millipore millex filter (0.45 lm) into thescattering cell (cuvette) whose outer surface was cleaned with aspecial type of cleaning paper. The dynamic light scatteringexperiment was carried out on a commercial LLS spectrometer

BI-200SM motor-driven goniometer equipped with BI-9000ATdigital autocorrelator and a cylindrical 22 mW uni-phaseHe–Ne laser (wavelength = 637 nm) at different temperatures

(15–60 �C) and pH (2–9) under different concentrations ofNaCl at a scattering angle of 90�.

3. Results

3.1. Fourier transforms infrared (FTIR) spectroscopy

The absorption peaks which were recorded in the spectra ofthree microgels samples are given in the Table 2. FTIR spec-

trum of G1 in Fig. 1 lacked peak of the carbon–carbon doublebond, which confirmed that polymerization occurred at thispoint since NIPAM and AAc, both monomers have C‚C

groups. The peaks of all the remaining functional groups ofmonomers are recovered in the spectrum of microgels, con-firming that polymerization has successfully occurred.

3.2. Effect of temperature

The hydrodynamic radius (Rh) of dilute dispersion of sampleG3 as a function of temperature at various pH values is shown

in Fig. 2. Microgel dispersion was found to be stable in the pHrange of 3.80–8.65 at 15–60 �C but it is unstable at pH = 2.25at a temperature greater than the volume phase transition of

microgels at this pH value. The increase in temperature and de-crease in pH cause hydrophobicity in the system. Under suchconditions, microgel particles combine with each other andaggregation takes place. That is why the Rh value suddenly in-

creases at pH 2.25 and temperature of 32 �C. Increase in pHincreases the stability of microgel dispersion but eliminates

isopropylacrylamide-co-acrylic acid) polymer microgels under variousf Chemistry (2013), http://dx.doi.org/10.1016/j.arabjc.2013.07.031

Table 1 The compositions of the prepared P(NIPAM-co-AAc) microgels.

Sample code NIPAM (g) AAc (g) BIS (g) APS (M) SDS (g) Water (mL)

G1 1.4 0.052 0.033 0.06 0.057 100

G2 1.4 0.079 0.033 0.06 0.057 100

G3 1.4 0.136 0.033 0.06 0.057 100

Figure 1 FTIR spectrum of P(NIPAM-co-AAc) microgel (G-1).

Figure 2 Plot of Rh as a function of temperature for P(NIPAM-

co-AAc) microgels (G3) at different pH values.

Figure 3 Plot of Rh of G3 sample as a function of pH for four

different temperatures.

Stability of poly(N-isopropylacrylamide-co-acrylic acid) polymer microgels under various conditions 3

the temperature sensitivity. Microgel particles exist in a swol-len state at pH greater than pKa value of AAc moiety anddo not show any temperature responsive behavior but at

pH < pKa, microgel is temperature sensitive. The reasoningbehind the swelling of microgel particle with increase in pHis the deprotonation of carboxylic groups present in the net-

work of microgel particles, as described previously (Farooqiet al., 2011a,b). A similar behavior was observed for sampleG1 and G2.

3.3. Effect of pH

The plot of Rh of microgel particle of dispersion G3 as afunction of pH of the medium at four different temperatures

Please cite this article in press as: Farooqi, Z.H. et al., Stability of poly(N-conditions of temperature, pH and salt concentration. Arabian Journal of

is given in Fig. 3. It is clear from this figure that size of micro-

gels increases as pH increases due to the deprotonation of theAAc (Snowden et al., 1996). Hence electrostatic repulsion be-tween the negatively charged carboxylate residues leads tothe swelling of microgel. Under these conditions, the hydrophi-

licity of the network increases and the microgels are capable ofuptaking large amounts of solvent, this also contributes to in-crease in the hydrodynamic radius of microgel (Fernandez-

Nieves et al., 2000).The microgel dispersion is stable in the pH range of 2–9 at

temperature ranging from 15 to 25 �C. The dispersion is unsta-

ble at pH 2.25 at 35 and 45 �C. The increase in Rh value at pH2.25 at high temperature is a clear indication of aggregation of

isopropylacrylamide-co-acrylic acid) polymer microgels under variousChemistry (2013), http://dx.doi.org/10.1016/j.arabjc.2013.07.031

Table 2 FTIR absorption bands of different functional groups of P(NIPAM-co-AAc) microgel G-1, G-2 and G-3.

Functional groups Observed peaks for G-1 (cm�1) Observed peaks for G-2 (cm�1) Observed peaks for G-3 (cm�1)

C–N 1148.00 1151.78 1154.56

CH2 (b) 1549.67 1535.53 1535.53

C‚O (amide) 1615.64 1621.83 1625.78

C–H (s) sp3 2971.35 2966.32 2954.43

N–H (s) 3307.00 3311.50 3308.47

Figure 5 Plot of Rh of sample G1 as a function of temperature in

the absence and presence of different NaCl concentrations at pH

2.99.

4 Z.H. Farooqi et al.

the dispersed particles (Naeem et al., 2012). The microgels atsuch a low pH and high temperature are not suitable candi-dates for different applications.

This aggregation behavior can be explained on the basis ofthe increase of polymer–polymer interaction at high tempera-ture in aqueous medium, and protonation of carboxylic

groups. These factors are main contributors to the aggregationof microgels.

3.4. Effect of salt concentration

Fig. 4 shows the plots of Rh as a function of temperature underdifferent concentrations of NaCl salt at pH 9.02. Variation in

the Rh of microgels is studied in 0.0, 0.05 and 0.1 M concentra-tions of NaCl of the surrounding medium. It is observed thatRh of microgel particles is greater in the absence of NaCl saltthan in its presence. Size of the microgel particle is also a func-

tion of the NaCl concentration and it decreases with the in-crease of salt concentration.

The decrease in size of microgel particles is because of the

poor quality of the given solvent and reduction in the electro-static repulsion. The sodium ions of salt have opposite chargesthan those of the polymer chains and enter into the network. So

they diminish the electrostatic repulsion. Then the particles col-lapse according to the extent of reduction of repulsion forcesamong the polymer chains. The value of Rh in the absence ofNaCl at 20 �C is 430.23 nm and that in 0.05 and 0.1 M NaCl

solutions at the same temperature is 156.12 and 133.56 nm,respectively. The decrease in Rh value with the addition of saltis due to the Debye screening as reported previously. The most

important feature of Fig. 4 is that the microgel dispersion is sta-ble within the experimental window of temperature at pH 9.02.These microgels are suitable candidates for biomedical, nano-

technological and catalytic applications in high ionic strength

Figure 4 Plot of Rh of sample G1 as a function of temperature in

the absence and presence of different NaCl concentrations at pH

9.02.

Please cite this article in press as: Farooqi, Z.H. et al., Stability of poly(N-conditions of temperature, pH and salt concentration. Arabian Journal o

at a temperature range of 15–65 �C. The microgel dispersionis not temperature sensitive in the presence and absence ofthe salt at pH 9.02.

At low pH, the effect of salt on the microgel size and colloi-dal stability is shown in Fig. 5. NaCl concentration was variedbetween 0.05 and 0.1 M. Below VPTT, on increasing tempera-

ture the change in Rh reveals a minor dependence on salt con-centration but after VPTT, Rh increases exponentially which isattributed to the formation of aggregates. The size of aggre-

gates increases with increase in salt concentration as shownin Fig. 5. AAc are not in ionized form at low pH. There isno electrostatic interparticle repulsion due to AAc. The coag-ulation of the colloidal particles is due to the hydrophobic

Figure 6 The graph of Rh of G1, G2 and G3 P(NIPAM-co-AAc)

microgel samples as a function of temperature at pH 3.01 in

deionized water.

isopropylacrylamide-co-acrylic acid) polymer microgels under variousf Chemistry (2013), http://dx.doi.org/10.1016/j.arabjc.2013.07.031

Figure 7 The graph of Rh of G1, G2 and G3 P(NIPAM-co-AAc)

microgel samples as a function of temperature at pH 4.72 in

deionized water.

Figure 8 The graph of Rh of G1, G2 and G3 P(NIPAM-co-AAc)

microgel samples as a function of temperature at pH 9 in deionized

water.

Figure 9 Plot of VPTT of G1, G2 and G3 samples as a function

of pH in deionized water.

Stability of poly(N-isopropylacrylamide-co-acrylic acid) polymer microgels under various conditions 5

interaction of the NIPAM in polymer of microgel. As for low-er salt concentration, this can be attributed to the well-known

‘salting-out’ effect (Park and Hoffman, 1993). With increase insalt concentration, the hydrophobic solvent quality increaseswhich lowers the VPTT as well as favors the aggregation. So

at temperature greater than VPTT, the interparticle interactiondominates and hydrogen bonding is formed between the car-boxyl group of the AAc side chains and the amide groups of

NIPAM which seems to favor the formation of larger aggre-gates. Fig. 5 also shows that the size of aggregates increasesremarkably for P(NIPAM-co-AAc) copolymer microgels with

Table 3 Rh of all samples of microgel at different pH of medium i

Microgel sample Rh(swollen) at 20 �C

pH= 3.01 pH= 4.72 pH=

G-1 132 204.32 445

G2 141 237.95 496

G3 165.32 345.42 632

Please cite this article in press as: Farooqi, Z.H. et al., Stability of poly(N-conditions of temperature, pH and salt concentration. Arabian Journal of

increasing ionic strength indicating that electrostatic repulsionhas a strong influence on the aggregation process.

3.5. Effect of acrylic acid moiety

Figs. 6–8 show the plots of Rh of all the three microgels sam-ples as a function of temperature at different pH values. Ob-served VPTT of all the prepared P(NIPAM-co-AAc)

microgel samples is higher than the VPTT of P(NIPAM)microgel (�32 �C) in water (Dhara et al., 2001). This increasein transition temperature is observed because of the incorpora-

tion of hydrophilic group AAc in polymer which increases theVPTT and makes its graph less steep (Fernandez-Nieves et al.,2000; Bradley et al., 2005). From the comparative analysis

study, we also observed that the Rh of sample G3 is the great-est of all samples at all pH, because it contains the highest con-tent of AAc than others. As AAc is strongly hydrophilic, so the

water content of hydrogel increases more than the others, con-sequently the size of this microgel increases (Varga et al.,2001).

The swelling/deswelling behavior of the prepared P(NI-

PAM-co-AAc) hydrogels as a function of temperature havingdifferent mole percentages of the acrylic acid at pH 3.01, 4.72and 9.02 is shown in Figs. 6–8, respectively. The Rh of all the

prepared microgels having different amounts of acrylic acid isenlisted in Table 3. Figs. 6 and 7 show that all the three sam-ples of microgel undergo phase transition on changing temper-

ature from 15 to 60 �C at acidic pH and pka of AAc. Underbasic conditions, no remarkable phase transition is visible.

Below the pKa value the acidic groups are in the protonatedform and have little or no effect on the volume phase transition

temperature. Above the pKa, the AAc moiety is deprotonatedand has a significant effect on the size and VPTT of microgeldue to the hydrophilic nature of the anion, columbic repulsion

n swollen and shrunken state.

Rh(shrunken) at 55 �C

9.02 pH= 3.01 pH= 4.72 pH= 9.02

45 70.65 427.45

61.56 106.23 504

91.53 119 627.8

isopropylacrylamide-co-acrylic acid) polymer microgels under variousChemistry (2013), http://dx.doi.org/10.1016/j.arabjc.2013.07.031

6 Z.H. Farooqi et al.

and osmotic swelling (Fernandez-Nieves et al., 2000; Ito et al.,1999).

At high pH, no phase transition occurs however, size in-

creases with the increase in AAc amount because at higherpH the microgel is less temperature responsive and the pH ef-fect is dominant in increasing its size (Kawasaki et al., 1997).

The comparison of VPTT of all the microgel samples at differ-ent pH is illustrated in Fig. 9 which is truly in accordance tothe above mentioned results and gives a proof of the stability

of microgels at different pH and temperatures.

4. Conclusions

The colloidal stability of P(NIPAM-co-AAc) microgels withdifferent AAc contents has been investigated in aqueous med-ium under various conditions of temperature, pH and NaCl

concentrations to find the range of application of these micro-gels in the field of nanotechnology, biomedical technology andcatalysis. High temperature and salt concentration, and lowpH decrease the stability of microgel system. P(NIPAM-co-

AAc) microgels are unstable below 2.25 pH and above 45 �Ctemperature. They cannot be used for aforementioned applica-tions outside boundary of these conditions. Stimuli sensitive

reversible swelling/deswelling behavior was not observed inmicrogels above pH 7. The microgel particles were in the swol-len state at low temperature and in the shrunken state at high

temperature. With increasing NaCl concentration, hydrody-namic radius of microgel particles decreases and VPTT shiftsto lower temperature. The size of hydrogel particles increaseswith the increase of AAc contents and VPTT is shifted to high-

er temperature because of its hydrophilic nature.

Acknowledgments

Then Higher Education Commission Pakistan is gratefully

acknowledged for the financial support under the US-PakistanScience and Technology Cooperative Program.

References

Bradley, M., Ramos, J., Vincent, B., 2005. Equilibrium and kinetic

aspects of the uptake of poly(ethylene oxide) by copolymer

microgel particles of N-isopropylacrylamide and acrylic acid.

Langmuir 21, 1209–1215.

Debord, S.B., Lyon, L.A., 2003. Influence of particle volume fraction

on packing in responsive hydrogel colloidal crystals. J. Phys. Chem.

B 107, 2927–2932.

Dhara, D., Nisha, C.K., Chatterji, P.R., 2001. Interpenetrating

networks of poly(N-isopropyl-acrylamide) with anionic and cat-

ionic polymers. Macromol. Chem. Phys. 202, 3617–3623.

Dowding, P.J., Vincent, B., Williams, E., 2000. Preparation and

swelling properties of poly(NIPAM) ‘‘Minigel’’ particles prepared

by inverse suspension polymerization. J. Colloid Interface Sci. 221,

268–272.

Farooqi, Z.H., Khan, A., Siddiq, M., 2011a. Temperature-induced

volume change and glucose sensitivity of poly[(N-isopropylacry-

lamide)-co-acrylamide-co-(phenylboronic acid)] microgels. Polym.

Int. 60, 1481–1486.

Farooqi, Z.H., Wu, W., Zhou, S., Siddiq, M., 2011b. Engineering of

phenylboronic acid based glucose-sensitive microgels with 4-vinyl-

Please cite this article in press as: Farooqi, Z.H. et al., Stability of poly(N-conditions of temperature, pH and salt concentration. Arabian Journal o

pyridine for working at physiological pH and temperature.

Macromol. Chem. Phys. 212, 1510–1514.

Fernandez-Nieves, A., Fernandez-Barbero, A., Vincent, B., de las

Nieves, F.J., 2000. Charge controlled swelling of microgel particles.

Macromolecules 33, 2114–2118.

Gorelikov, I., Field, L.M., Kumacheva, E., 2004. Hybrid microgels

photoresponsive in the near-infrared spectral range. J. Am. Chem.

Soc. 126, 15938–15939.

Ito, S., Ogawa, K., Suzuki, H., Wang, B., Yoshida, R., Kokufuta, E.,

1999. Preparation of thermosensitive submicrometer gel particles

with anionic and cationic charges. Langmuir 15, 4289–4294.

Jones, C.D., Lyon, L.A., 2000. Synthesis and characterization of

multiresponsive core–shell microgels. Macromolecules 33, 8301–

8306.

Jones, C.D., Lyon, L.A., 2003. Dependence of shell thickness on core

compression in acrylic acid modified poly(N-isopropylacrylamide)

core/shell microgels. Langmuir 19, 4544–4547.

Kawasaki, H., Sasaki, S., Maeda, H., 1997. Effect of pH on the volume

phase transition of copolymer gels of N-isopropylacrylamide and

sodium acrylate. J. Phys. Chem. B 101, 5089–5093.

Kim, J., Serpe, M.J., Lyon, L.A., 2004. Hydrogel microparticles as

dynamically tunable microlenses. J. Am. Chem. Soc. 126, 9512–

9513.

Lee, J., Park, J.C., Song, H., 2008. A nanoreactor framework of a

Au@SiO2 yolk/shell structure for catalytic reduction of p-nitro-

phenol. Adv. Mater. 20, 1523–1528.

Lopez-Leon, T., Elaıssari, A., Ortega-Vinuesa, J.L., Bastos-Gonzalez,

D., 2007. Hofmeister effects on poly(NIPAM) microgel particles:

macroscopic evidence of ion adsorption and changes in water

structure. Chem. Phys. Chem. 8, 148–156.

Mohan, M.Y., Vimala, K., Thomas, V., Varaprasad, K., Sreedhar, B.,

Bajpai, S.K., Mohana Raju, K., 2010. Controlling of silver

nanoparticles structure by hydrogel networks. J. Colloid Interface

Sci. 342, 73–82.

Morris, G.E., Vincent, B., Snowden, M.J., 1997. Adsorption of lead

ions onto N-isopropylacrylamide and acrylic acid copolymer

microgels. J. Colloid Interface Sci. 190, 198–205.

Murthy, N., Xu, M., Schuck, S., Kunisawa, J., Shastri, N., Frechet,

J.M.J., 2003. A macromolecular delivery vehicle for protein-based

vaccines: acid-degradable protein-loaded microgels. Proc. Natl.

Acad. Sci. 100, 4995–5000.

Naeem, H., Farooqi, Z., Shah, L., Siddiq, M., 2012. Synthesis and

characterization of p(NIPAM-AA-AAm) microgels for tuning of

optical properties of silver nanoparticles. J. Polym. Res. 19, 1–10.

Nilsson, P., Hansson, P., 2005. Ion-exchange controls the kinetics of

deswelling of polyelectrolyte microgels in solutions of oppositely

charged surfactant. J. Phys. Chem. B 109, 23843–23856.

Nisato, G., Munch, J.P., Candau, S.J., 1999. Swelling, structure, and

elasticity of polyampholyte hydrogels. Langmuir 15, 4236–4244.

Park, T.G., Hoffman, A.S., 1993. Sodium chloride-induced phase

transition in nonionic poly(N-isopropylacrylamide) gel. Macro-

molecules 26, 5045–5048.

Retama, J.R., Lopez-Ruiz, B., Lopez-Cabarcos, E., 2003. Microstruc-

tural modifications induced by the entrapped glucose oxidase in

cross-linked polyacrylamide microgels used as glucose sensors.

Biomaterials 24, 2965–2973.

Snowden, M.J., Chowdhry, B.Z., Vincent, B., Morris, G.E., 1996.

Colloidal copolymer microgels of N-isopropylacrylamide and

acrylic acid: pH, ionic strength and temperature effects. J. Chem.

Soc. Faraday Trans. 92, 5013–5016.

Sun, H.-Q., Zhang, L., Li, Z.-Q., Zhang, L., Luo, L., Zhao, S., 2011.

Interfacial dilational rheology related to enhance oil recovery. Soft

Matter 7, 7601–7611.

Varga, I., Gilanyi, T., Meszaros, R., Filipcsei, G., Zrınyi, M., 2001.

Effect of cross-link density on the internal structure of poly(N-

isopropylacrylamide) microgels. J. Phys. Chem. B 105, 9071–9076.

isopropylacrylamide-co-acrylic acid) polymer microgels under variousf Chemistry (2013), http://dx.doi.org/10.1016/j.arabjc.2013.07.031

Stability of poly(N-isopropylacrylamide-co-acrylic acid) polymer microgels under various conditions 7

Zhang, J., Xu, S., Kumacheva, E., 2004. Polymer microgels: reactors

for semiconductor, metal, and magnetic nanoparticles. J. Am.

Chem. Soc. 126, 7908–7914.

Please cite this article in press as: Farooqi, Z.H. et al., Stability of poly(N-conditions of temperature, pH and salt concentration. Arabian Journal of

Zhang, Y., Guan, Y., Zhou, S., 2006. Synthesis and volume phase

transitions of glucose-sensitive microgels. Biomacromolecules 7,

3196–3201.

isopropylacrylamide-co-acrylic acid) polymer microgels under variousChemistry (2013), http://dx.doi.org/10.1016/j.arabjc.2013.07.031