7698
Langmuir 2008, 24, 7698-7703
Inverse Microemulsion Polymerization of Sterically Stabilized Polyampholyte Microgels Beng S. Ho,† Beng H. Tan,‡ Jeremy P. K. Tan,†,# and Kam C. Tam*,§ School of Mechanical and Aerospace Engineering, Nanyang Technological UniVersity, 50, Nanyang AVenue, Singapore 639798, Institute of Materials Research and Engineering, Agency for Science Technology and Research, 3, Research Link, Singapore 117602, Institute of Bioengineering and Nanotechnology, Agency for Science Technology and Research, 31 Biopolis Way, The Nanos, #04-01, Singapore 138669, and Department of Chemical Engineering, UniVersity of Waterloo, 200 UniVersity AVenue West, Waterloo, Ontario, Canada N2L 3G1 ReceiVed December 10, 2007. ReVised Manuscript ReceiVed February 22, 2008 Polyampholyte microgels consisting of various compositions of poly(methacrylic acid) and poly(2-(dimethylamino)ethyl methacrylate) (PMAA-PDMA) cross-linked with allyl methacrylate (AM) were synthesized via the inverse microemulsion polymerization (IMEP) technique. To improve colloidal stability at the isoelectric point (IEP), steric stabilization via the grafting of poly(ethylene glycol) methyl ether methacrylate (PEGMA) on the surface of the microgel was performed. Potentiometric and conductometric titration showed good agreement between the targeted and experimental compositions of the microgel systems. The microgel swelled at low and high pH and possessed a compact structure near the IEP, and the diameter were in good agreement with data from the transmission electron microscopic (TEM) analyses. With increasing pH, the mobility decreased from +2 m2s-1V1 at pH 2 to -2 m2s-1V1 at pH 10. An empirical relationship describing the PMAA composition and IEP was proposed, where the IEP decreased with increasing PMAA content. The microgel exhibited thermal-responsive properties at high pH, which is dictated by the lower critical solution temperature of PDMA.
1. Introduction Microgels are colloidal dispersions of intramolecularly crosslinked polymeric chains. In the past several decades, increasing attention has been focused on the synthesis and applications of novel microgel systems. These systems have received increasing attention due to their potential applications in drug delivery,1,2 fabrication of photonic crystals,3 template-based synthesis of inorganic nanoparticles,4 and separation technologies.5,6 pHresponsive microgels based on either acidic or basic monomers are attractive systems, as they can be designed with the desired pH-responsive properties for use in biomedical and biological applications, such as delivery vehicles for protein-loaded vaccines.7 Zwitterionic polymers or polyampholytes contain both positive and negative charges along the same polymeric backbone. Due to the presence of opposite charges, the dilute aqueous solution properties of these polymers are complex and are governed by intrachain electrostatic interactions. Numerous publications on the synthesis of random linear zwitterionic copolymers and diblock polyampholytes systems have appeared recently;8–11 * Corresponding author. E-mail:
[email protected]. † Nanyang Technological University. ‡ IMRE, Agency for Science Technology and Research. # IBN, Agency for Science Technology and Research. § University of Waterloo. 80.
(1) Das, M.; Mardyani, S.; Chan, W.; Kumacheva, E. AdV. Mater. 2005, 18,
(2) Nayak, S.; Lee, H.; Chmielewski, J.; Lyon, L. A. J. Am. Chem. Soc. 2004, 126(33), 10258. (3) Xu, S.; Zhang, J.; Paquet, C.; Lin, Y.; Kumacheva, E. AdV. Funt. Mater. 2003, 13, 468. (4) Zhang, J. G.; Xu, S. Q.; Kumacheva, E. J. Am. Chem. Soc. 2004, 126(25), 7908. (5) Bromberg, L.; Temchenko, M.; Hatton, T. A. Langmuir 2003, 19, 8675. (6) Snowden, M. J.; Thomas, D.; Vincent, B. Analyst 1993, 118(11), 1367. (7) Murthy, N.; Xu, M. C.; Schuck, S.; Kunisawa, J.; Shastri, N.; Frechet, J. M. J. Proc. Natl. Acad. Sci. U.S.A. 2003, 100(9), 4995. (8) Pispas, S.; Hadjichristidis, N. J. Polym. Sci. Part A 2000, 38(20), 3791.
however, studies on stable (noncoagulating) polyampholyte microgels are scarce. Schulz et al. prepared and characterized a series of spherical latex particles with functionalized polyampholytes on the surface, resulting in a range of isoelectric points (IEPs), and they coagulated at around the IEP. However by adjusting the pH values, their surface charge increased and the latexes were redispersed.12 Armes and co-workers reported on the synthesis and physical properties of acid-swellable poly (2(diethylamino)ethyl methacrylate) (PDEA) microgels, which are sterically stabilized by reactive macromonomers to achieve colloidal stability.13 Such systems are interesting and worthy of further study because they are able to maintain a robust internal microstructure under all pH conditions. Recent studies on new polyampholyte microgels were motivated by their stimuli-responsive character as demonstrated by their ability to respond to various external stimuli, including changes in temperature,14–16 pH,7,17–19 and ionic strength of the surrounding medium.20 There are, however, very few reported studies on the synthesis of stimuli-responsive polyampholyte (9) Lowe, A. B.; Billingham, N. C.; Armes, S. P. Macromolecules 1998, 31, 5991. (10) McCormick, C. L.; Salazer, L. C. Marcomolecules 1992, 25, 1896. (11) Hahn, M.; Koltz, J.; Ebert, R.; Schmolke, B.; Philipp, S.; Kudaibergenov, V.; Sigitov, V.; Bekturov, E. A. Acta Polym. 1989, 40, 331. (12) Schulz, D. F.; Gisler, T.; Borkovec, M.; Sticher, H. J. Colloid Interface Sci. 1993, 164, 88. (13) Amalvy, J. I.; Unali, G. F.; Li, Y.; Granger-Bevan, S.; Armes, S. P. Langmuir 2004, 20, 4345. (14) Hoare, T.; Pelton, R. Marcomolecules 2004, 37, 2544. (15) Kuckling, D.; Vo, C. D.; Wohlrab, S. E. Langmuir 2002, 18(11), 4263. (16) Tam, K. C.; Wu, X. Y.; Pelton, R. H. J. Polym. Sci. Part A 1993, 31(4), 963. (17) Tan, B. H.; Ravi, P.; Tam, K. C. Macromol. Rapid Commun. 2006, 27, 522. (18) Tan, B. H.; Ravi, P.; Tan, L. N.; Tam, K. C. J. Colloid Interface Sci. 2007, 309, 453. (19) Amalvy, J. I.; Wanless, E. J.; Li, Y.; Michailidou, V.; Armes, S. P. Langmuir 2004, 20, 8992. (20) Tan, B. H.; Tam, K. C.; Lam, Y. C.; Tan, C. B. Langmuir 2004, 20, 11380.
10.1021/la703852p CCC: $40.75 2008 American Chemical Society Published on Web 06/27/2008
InVerse Microemulsion Polymerization of Microgels
microgels.12,13,21 Neyret and Vincent reported on the use of a microemulsion polymerization technique to prepare polyampholyte microgel by copolymerizing an anionic monomer, sodium 2-acrylamido-2-methylpropanesulfonate (NaAMPS), and a cationic monomer, (2-(methacryloyxy)trimethylammonium chloride) (MADQUAT), together with a cross-linking agent, N,N′methylenebisacrylamide (BA).22 Kumacheva et al. prepared polyampholyte microgels with different fractions of acrylic acid (AA) and N-vinylimidazole (VI) monomers.23 The microgel exhibited dramatic swelling at both high and low pH values but shrank at pH ranging from 4 to 7 due to electrostatic attraction between charged AA and VI moieties. An increase in the molar ratio of anionic-to-cationic residues caused the IEP to shift toward lower values of pH because the number of COO- groups exceeded the number of NH+ groups. Thus, increased acidity was required to protonate excess COO- groups (that were not neutralized by NH+ moieties) to attain the isoelectric point.23 Very recently, our group reported on the synthesis of a pH-responsive crosslinked microgel, poly(methacrylic acid)-co-poly(2-(diethylamino)ethyl methacrylate) (PMAA-PDEA) that is sterically stabilized by poly(ethylene glycol) methyl ether methacrylate (PEGMA). These microgel particles were prepared via the conventional emulsion polymerization. The cross-linked microgel PMAA-PDEA showed a gradual increase in hydrodynamic radius (Rh) in aqueous medium at low and high pH due to the increase in osmotic pressure within the microgel. At intermediate pH, the microgel became more compact due to overall charge neutralization near the IEP.17,18 Bradley et al. prepared biocompatible, polyampholyte microgel particles by acid hydrolysis of tert-butyl groups on (2-diethylamino)ethyl methacrylate-cotert-butyl methacrylate microgel particles to produce (2-diethylamino)ethyl methacrylate-co-methacrylic acid microgel particles. The swelling properties and isoelectric point pH depended on the monomer composition.24 Because of their possible applications in biomedical science and biotechnology, various composition of the pH- and thermalresponsive polyampholyte microgels consisting of poly(meth acrylic acid) and poly(2-(dimethylamino)ethyl methacrylate) (PMAA-PDMA) cross-linked with allyl methacrylate (AM) were synthesized. These microgel systems can potentially be used for drug and protein delivery applications because of the stability of the microgel and the biocompatibility of PMAA and PDMA chains.25,26 The PDMA segments could be protonated to yield positive charges at low pH, and the slightly hydrophobic PMAA segments acquire negative charges at high pH. Since both segments have different pKa values and different chain lengths, the hydrophile-lipophile balance (HLB) values of the microgel at high or low pH are different. Attempts to prepare these microgels using the conventional seeded emulsion polymerization technique in aqueous environment were unsuccessful as the 2-(dimethylamino)ethyl methacrylate (DMA) monomer is rather hydrophilic, and it polymerizes in the bulk aqueous solution, instead of the micellar core. As a consequence, a heterogeneous colloidal dispersion was produced. To overcome this problem, the inverse microemulsion (water-in-oil) polymerization technique (IMEP) was adopted as it is more suitable for polymerizing (21) Kihara, N.; Adachi, Y.; Nakao, K.; Fukutomi, J. Appl. Polym. Sci. 1998, 69, 1863. (22) Neyret, S.; Vincent, B. Polymer 1997, 38(25), 6129. (23) Das, M.; Kumacheva, E. Colloid Polym. Sci. 2006, 284, 1073. (24) Bradley, M.; Vincent, B.; Burnett, G. Aust. J. Chem. 2007, 60, 646. (25) Wetering, P. V. D.; Cherng, J.-Y.; Talsma, H.; Hennink, W. E. J. Controlled Release 1997, 49, 59. (26) Torres-Lugo, M.; Garcıa, M.; Record, R.; Peppas, N. A. J. Controlled Release 2002, 80, 197.
Langmuir, Vol. 24, No. 15, 2008 7699
Figure 1. Chemical structure of cross-linked MAA-DMA microgel with AM.
hydrophilic monomers.27 The pH-responsive behavior of these microgels was elucidated by potentiometric and conductometric titrations, dynamic light scattering (DLS), ζ-potential, and transmission electron microscopic (TEM) techniques.
2. Experimental Section Materials. Methacrylic acid (MAA) (99%), 2-(dimethylamino)ethyl methacrylate (DMA) (99%), allyl methacrylate (AM), poly(ethylene glycol) methyl ether methacrylate (PEGMA) (average molecular weight of ∼300 Da), sodium persulfate (Na2O8S2), Brij 96 (polyoxyethylene(10) oleyl ether, C18E10; HLB ∼ 12.4), and Brij 92 (polyoxyethylene(2) oleyl ether, C18E2; HLB ∼ 4.9) were all purchased from Aldrich. The monomers were used as received. Brij 96 and Brij 92 were used without further purification as emulsifiers for the inverse microemulsion polymerization. The emulsifier was prepared by mixing 4.4 g of Brij 96 and 14.7 g of Brij 92 to yield a HLB ∼ 7 that possessed a phase inversion temperature of 65 °C.28 Other chemicals, such as sodium hydroxide, hydrochloride acid, sodium chloride, n-hexane, and acetone were purchased from Merck and used as received. Deionized water used was from Millipore Alpha-Q purification system equipped with a 0.22 µm filter and had a resistivity of 18.2 µS/cm. The chemical structure of the cross-linked PMAA-PDMA microgel is schematically shown in Figure 1. The microgels are designated as xM-yD, where x and y correspond to the mole percent of PMAA and PDMA, respectively. Six different microgels were synthesized, 70M-30D, 60M-40D, 50M-50D, 40M-60D, 30M-70D, and 20M-80D, and the amount of cross-linker was fixed at 2 wt % AM. Polymer Synthesis. The total emulsifier content was kept constant at 6% for all the emulsion systems. The surfactant mixture were prepared in 150 g of n-hexane and homogenized for 5 min. A typical procedure for the synthesis of microgels consisting of 20 mol % PMAA, 80 mol % PDMA, and 2 wt % AM is as follows: A monomer mixture of 14.57 g (1.72 g of PMAA, 12.56 g of PDMA, and 0.29 g (27) Kumar, P.; Mittal, K. L. Handbook of Microemulsion Science and Technology; Marcel Dekker, Inc., New York. 1999. (28) Lehnert, S.; Tarabishi, H.; Leuenerger, H. Colloids Surf. 1994, 91, 227.
7700 Langmuir, Vol. 24, No. 15, 2008
Ho et al. Table 1. Typical Theoretical and Actual Monomer Ratios Calculated from Titration of Cross-Linked MAA-DMA Microgel with Varying Monomer Ratios PMAA:PDMA ratio
Figure 2. Potentiometric and conductometric titration of 0.02 wt % of microgel concentration of 70M-30D (filled symbols) and 30M-70D (open symbols) with 0.1 M HCl at 25 °C. Squares represent conductivity and circles represent pH.
of AM) was mixed in 150 g of distilled-deionized water in a glass beaker and added to the surfactant mixture. The final mixture was then added to a reaction vessel (500 mL four-neck flask) equipped with a condenser and an overhead mechanical stirrer operating at 250 rpm, and the temperature was raised to 65 °C. After the first hour, the initiator solution comprising 0.45 g of sodium persulfate (Na2O8S2) and 8 g of distilled-deionized water was conveyed to the reaction vessel. The reaction was left to proceed for 2 h, after which another initiator feed mixture comprising 0.15 g sodium persulfate and 3 g distilled-deionized water, together with 5.3 g of PEGMA (Mn ) 300 Da), equivalent to 5 mol % of the total feed monomer, were added to the reaction vessel. Finally, the reaction was left to proceed for another three hours and the reaction mixture was cooled and filtered through a 200-mesh nylon cloth. Stable microgels were obtained with only a small amount (
