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Synthesis and Characterization of Thermosensitive PNIPAM Microgels Covered with Superparamagnetic γ-Fe2O3 Nanoparticles Jorge Rubio-Retama,*,† Nikolaos E. Zafeiropoulos,*,† Caterina Serafinelli,† Rosana Rojas-Reyna,† Brigitte Voit,† E. Lopez Cabarcos,‡ and Manfred Stamm† Leibniz-Institut fu¨r Polymerforschung Dresden, Hohe Strasse 6, Dresden 01069, Germany, and Departamento Quı´mica Fı´sica II, Facultad de Farmacia, UniVersidad Complutense, 28040 Madrid, Spain ReceiVed April 5, 2007. In Final Form: July 16, 2007 In the present study we report a facile and reproducible method of preparing magnetic thermosensitive hybrid material based on P(NIPAM) microgels covered with γ-Fe2O3 nanoparticles of 6-nm size. The iron oxide nanoparticles provided magnetic response to the microgels. In addition, the presence of the magnetic nanoparticles on the microgels altered their swelling behavior and shifted their volume phase transition temperature to higher values. In particular, for inorganic shells with 18% (w/w) of magnetic nanoparticles the volume phase transition of the microgels was shifted from 36 to 40 °C. In contrast, for shells consisting of 38% (w/w) magnetic nanoparticles the volume phase transition of the microgels was almost blocked, thus indicating that the microgel thermal response was strongly affected by the presence of the inorganic nanoparticles. The synthesized thermosensitive magnetic microgels are envisaged to be ideal for potential applications as thermosensitive targeted drug delivery systems.
1. Introduction Hydrogels are interesting materials with intriguing properties due to their capacity to undergo large volume transition in aqueous solution in response to tiny changes in the environmental conditions.1-3 The large number of water molecules that solvate the polymer chains yields systems with rubbery properties that resemble natural living tissues.4-8 The phenomenon of gel volume transition in response to external stimuli (e.g., temperature, pH, ionic strength, or electric field)9-11 has prompted increased scientific interest in investigating gels as potential actuators. A thermo-induced volume phase transition appears in hydrogels based on weakly cross-linked polymers, which exhibit a lower critical solution temperature (LCST). Microgels based on poly(N-isopropyl acrylamide), (PNIPAM), are very promising materials for biomedical applications such as drug delivery systems since they exhibit an LCST11-13 at around 32 °C and are biocompatible.14 For this reason poly(NIPAM) hydrogels have commonly been referred to as smart materials for drug * Corresponding authors. E-mail:
[email protected];
[email protected]. † Leibniz-Institut fu ¨ r Polymerforschung Dresden. ‡ Universidad Complutense. (1) D. Rossi, K.; Kajiwara, Y.; Osada, A.; Yamauchi, A. Polymer Gels; New York: Plenum Press, 1991. (2) Bastide, J.; Candau, S. J. In Physical Properties of Polymeric Gels; Addad, C., Ed.; New York: Wiley, 1996. (3) Shibayama, M. Macromol. Chem. Phys. 1998, 1, 199. (4) Flory, P. J. Principles of Polymer Chemistry; Cornell University Press: New York, 1975. (5) Doi, M. Introduction to Polymer Physics; Oxford University Press: New York, 1996. (6) Shibayama, M.; Takahashi, H.; Nombra, S. Macromolecules 1995, 28, 6860. (7) Suzuki, A.; Tanaka, T. Nature 1990, 346, 345. (8) Rubio-Ratema, J.; Lo´pez-Cabarcos, E.; Lo´pez-Ruiz, B. Biomaterials C. 2003, 24, 2965. (9) Daly, E.; Saunders, B. R. Langmuir 2000, 16, 5546. (10) Nerapusri, V.; Keddie, J. L.; Vincent, B.; Busnak, I. A. Langmuir 2006, 22, 5036. (11) Lo´pez-Leon, T.; Ortega-Vinuesa, J. L.; Bastos-Gonzalez, D.; Elassari, A. J. Phys. Chem. B 2006, 110, 4621. (12) Fernandez-Nieves, A.; Fernandez-Barbero, A.; Vincent, B.; De las Nieves, F. J. J. Chem. Phys. 2003, 119, 10383. (13) Meunier, F.; Elaı¨ssari, A.; Pichot, C. Polym. AdV. Technol. 1994, 6, 489. (14) Vihola, H.; Laukkanen, A.; Valtola, L.; Tenhu, H.; Hirvonen, J. Biomaterials 2005, 26, 3055.
delivery applications, because they could respond to thermal stimulus, e.g., local hyperthermia produced by a tumor tissue,15 delivering drugs locally and only when needed.15-21 However, the response time in bulk gels is slow, prompting microgels to be considered as better systems when shorter response times are required.22 In addition, the submicrometer size of the microgels allows intravenous dispensation, hence, extending their applicability and versatility.16 In such applications the external control on the microgels is necessary in order to target specific tissues and to minimize toxic side effects.15-21 For this reason hybrid materials containing magnetic nanoparticles have received a lot of interest during the last few years; the magnetic functionality can be used to guide the microgels in particular parts, thus opening up the possibility of their use as targeted dug delivery systems. Until today such systems have received considerable interest in the literature, and various approaches have been reported for their preparation. Kondo et al.23,25 synthesized PNIPAM microgels (15) Arnold, I.; Freeman, M. D.; Mayhew, E. Cancer 1986, 58, 583. (16) Schmaljohann, D. AdV. Drug DeliVery ReV. 2006, 58, 1655. (17) Wei, H.; Zhang, X.; Cheng, C.; Cheng, X.; Zhou, R. X. Biomaterials 2007, 28, 99. (18) Na, K.; Park, J.; Kim, S.; Sun, B.; Woo, D.; Chung, H.; Park, K. Biomaterials 2006, 27, 5951. (19) Liu, Y.; Lu¨, J. Biomaterials 2006, 27, 4016. (20) Dube, D.; Francis, M.; Leroux, J. C.; Winnik, F. M. Bioconjugate Chem. 2002, 13, 685. (21) Ohya, S.; Nakayama, Y.; Matsuda, T. Biomacromolecules 2001, 2, 856. (22) Wu, X.; Pelton, R. H.; Hamielec, A. E.; Woods, D. R.; McPhee, W. Colloid Polym. Sci. 1994, 272, 467. (23) Kondo, A.; Fukuda, H. J. Ferment. Bioeng. 1997, 84, 337. (24) Chang, Y.; Su, Z. Mater. Sci. Eng. 2002, 333, 155. (25) Kondo, A.; Kamura, H.; Higashitani, K. Appl. Microbiol. Biotechnol. 1994, 41, 99. (26) Hussain, S. M.; Hess, K. L.; Gearhart, J. M.; Geiss, K. T.; Schlager, J. J. Toxicol. Vitro 2005, 19, 975. (27) Ronald, A.; Grady, B.; Kopke, R.; Dormir, K. Colloid Surf., A 2007. In press. (28) Feeny, J. P.; Napper, D. H.; Gilbert, R. Macromolecules 1989, 20, 2922. (29) Pelton, R. H.; Chivante, P. Colloid Surf. 1986, 20, 247. (30) Saunders, B. R.; Vincent, B. AdV. Colloids Interface Sci. 1999, 80, 1. (31) McPhee, W.; Tam, K. C.; Pelton, R. H. J. Colloid Interface Sci. 1993, 156, 24. (32) Seung-Jun, L.; Jong-Ryu, J.; Sung-Chul, S.; Jin-Chul, K.; Jong-Duk, K. J. Magn. Magn. Mater. 2004, 147, 6282. (33) Horkay, F.; Basser, P. J.; Hecht, A. M.; Geissler, E. Macromolecules 2000, 33, 8329.
10.1021/la7009594 CCC: $37.00 © 2007 American Chemical Society Published on Web 08/25/2007
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Figure 1. (A) SEM micrograph of PNIPAM microgels. (B) P(NIPAM-AA) microgels. (C) Fe18P(NIPAM-AA) and Fe38P(NIPAM) microgels. (Insets) Size distribution of the respective microgels in aqueous solution at 25 °C.
using aqueous ferrofluids as reaction media. This synthesis method resulted in magnetic nanoparticles immobilized inside PNIPAM microgels.23,25 The disadvantage of this method lies on the low inorganic content of the microgels, which is defined by the concentration of magnetic nanoparticles in the ferrofluid, usually lower than 10% (w/w). Different routes have been reported by Pichot and co-workers.13,45 Pichot et al. prepared core-shell magnetic microgels with PNIPAM as the shell using a precipitation polymerization of NIPAM and styrene.48 In a second approach (34) Lindsley, D. Experimental Studies of Oxide Minerals. In Oxide Minerals (formerly known as Short Course Notes); Rumble, D., III, Ed.; Reviews in Mineralogy, Vol. 3; Mineralogical Society of America: Washington, D.C., 1976; p L-18. (35) Yu, S.; Chow, G. M. J. Mater. Chem. 2004, 14, 2781. (36) Fan, X.; Zhang, G.; Zhang, F. Mat. Sci. Eng. 2007 (online version). (37) Jia, Z.; Yujun, W.; Yangcheng, L.; Jingyu, M.; Guangsheng, L. React. Funct. Polym. 2006, 66, 1552. (38) Krazt, K.; Hellweg, T.; Eimer, W. Colloid Surf., A 2000, 170, 137. (39) Hellweg, T.; Dewhurst, C. D.; Eimer, W.; Krazt, K. Langmuir 2004, 11, 4330. (40) Lo´pez-Cabarcos, E.; Mecerreyes, D.; Sierra-Martin, B.; Romero-Cano, M. S.; Strunz, P.; Fe´rnandez-Barbero, A. Phys. Chem. Chem. Phys. 2004, 6, 1396. (41) Akcora, P.; Zhang, X.; Varughese, B.; Briber, R. M.; Kofinas, P. Polymer 2005, 46, 5194. (42) Bhattacharya, S.; Eckert, F.; Boyko, V.; Pich, A. Small 2007. http:// dx.doi.org/10.1002/smll200600613. (43) Pich, A.; Bhattacharya, S.; Lu, Y.; Boyko, V.; Adler, H. J. Langmuir 2004, 20, 10706. (44) Suzuki, D.; Kawaguchi, H. Colloid Polym. Sci. 2006, 284, 1443. (45) Sauzedde, F.; Elaissari, A.; Pichot, C. Colloid Polym. Sci. 1999, 277, 1041. (46) Dutta, D. P.; Sharma, G.; Rajarajan, A.; Yusuf, S. M.; Dey, G. K. Chem. Mater. 2007, 19, 1221. (47) Suber, L.; Fiorani, D.; Scavia, G.; Imperatori, P. Chem. Mater. 2007, 19, 1509. (48) Elaissari, A.; Rodriguez, M.; Menuir, F.; Herve, C. J. Magn. Magn. Mater. 2001, 225, 127.
positively charged polystyrene-PNIPAM seed particles were coated with negatively charged iron oxide particles and were subsequently encapsulated with copolymerizing NIPAM with itacomic acid.45 In both approaches the authors obtained superparamagnetic, monodisperse submicrometer microspheres with different magnetite loadings and with temperature sensitivity. In a different approach, Kawaguchi and co-workers recently prepared poly(glycidyl methacrylate (PGMA-PNIPAM) coreshell microgels that were modified with ionic groups and used these microgels for a guided deposition of iron oxides in the charged areas.44 Finally, very recently also Pich and co-workers prepared microgels based on poly(vinylcaprolactam) with magnetite nanoparticles entrapped inside. The method reported by Pich et al. yielded pH- and temperature-responsive materials with volume phase transition shifted from 33 to 36 °C. The strategy followed by Pich et al. was based on the synthesis of magnetic nanoparticles “Via coprecipitation” in the presence of previously synthesized microgels. Nevertheless this method yielded microgels with magnetic nanoparticles randomly distributed inside.23,25 The present study describes a facile route for preparing monodisperse microgels with their surfaces decorated with γ-Fe2O3 nanoparticles. Herewith we discus the effect of the presence of such an inorganic shell and how it modifies the swelling of the hybrid material and alters the volume phase transition of microgels. The present work, together with the previously published work by the Pich, Kondo, Kawagushi, and Pichot research groups, permits a better understanding of the influence of the magnetic nanoparticle localization in the swelling and thermal behavior of the microgels. In addition, the prepared
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Figure 2. TEM micrograph of Fe18P(NIPAM) microgels. (Inset) SAED pattern of the iron oxide nanoparticles that cover the microgels.
Figure 4. (A) Aqueous dispersion of Fe18P(NIPAM-AA) microgels in absence of magnetic field. (B) Response of the microgels after applying a magnet of 0.24 T.
Figure 3. TEM micrograph of the Fe38P(NIPAM) microgels with 38% (w/w) of inorganic iron oxide.
hybrid microgels exhibit a volume phase transition at 40 °C, which permits their potential use in vivo as carriers for targeted drug delivery since the temperature of healthy tissue is 36.6 °C. 2. Experimental Section The monomer N-isopropyl-acrylamide, the cross-linker N,Nmethylene-bis-acrylamide, the initiator, ammonium persulfate (APS), and sodium poly(styrene sulfonate) (70000 g/mol) were purchased from Aldrich. The iron precursors (FeCl3‚6H2O and FeCl2‚4H2O) were purchased from Panreac. All chemicals were used without further purification. A commercial NdFeB magnet with a magnetic field of 0.24 T was purchased from www.conrad.de. The microgel particles were studied by using scanning electron microscopy in a JEOL (JSM-6400) microscope, coupled with a detector for elemental analysis. Transmission electron microscopy (TEM) was performed using a JEOL-2000FX microscope operating at 200 kV. Dynamic light-scattering experiments (DLS) were carried out to examine the evolution of the particle size at the volume phase transition using a Malvern NanoZS system equipped with a He-Ne laser working at 632.8 nm. The time correlation function of the scattered intensity, g(t) ) 〈I(0)I(t)〉, was measured, and the mean hydrodynamic radius was obtained as a function of temperature using cumulant analysis. The suspension of microgels was diluted to a concentration of 0.02% (w/w) to prevent multiple scattering and to diminish colloidal interactions. The charge of the microgels was determined using a Particle Charge Detector model PCD 03 µMu¨tek. The negative charge
Figure 5. Magnetization curve for Fe18P(NIPAM-AAS) microgels (black points) and Fe38P(NIPAM-AAS) microgels (green points) at room temperature. of the microgels was inferred from the amount of poly(diallyldimethyl-ammonium-chloride) needed to reach the isoelectric point of a 0.1% (w/w) microgel dispersion. Colloidal stability studies were carried out by measuring the sedimentation velocity at 3000 RPM and pH 7, using a Lumisizer Lum GmbH, Germany.
3. Results and Discussion The multifunctional microgels were synthesized as follows. P(NIPAM) microgels were prepared by surfactant free radical polymerization29-31 of 50 mL of an aqueous solution formed by N-isopropyl-acrylamide (0.1 M, 550 mg) and N,N-methylenebis-acrylamide (0.007 M, 50 mg) at 70 °C using 250 mg of ammonium persulfate as initiator. With the aim of creating a carboxylic group-rich shell in which the iron nanoparticles could be deposited, we added sodium acrylate (0.01 M, 35 mg) 15 min after starting the reaction. This resulted in microgels enriched with carboxylic groups, which were preferentially distributed on the surface. As a result, the superficial negative charge of the
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Figure 6. Experimental mean particle diameter vs temperature for different microgels. (Inset) d(mean diameter)/d(temperature) as a function of the temperature (blue, neat P(nipam) microgels; red, PNIPAM-ASS microgels; black, Fe18PNIPAM-ASS microgels; green, Fe38PNIPAM-ASS microgels). Table 1. SAED Data for the Magnetic Nanoparticles radius (mm) ED results d (Å) d-spacing of cubic γ-Fe2O324 crystalline plane (hlk)
1
2
3
4
5
6
7
8
6.7 2.95 2.95 (220)
7.9 2.51 2.51 (311)
10.9 1.82 1.82 (421)
13.0 1.53 1.52 (521)
13.6 1.47 1.47 (440)
16.0 1.25 1.26 (622)
18.0 1.11 1.11 (642)
19.2 1.04 1.04 (800)
microgels increased from 4.7 C/g for poly(NIPAM) microgels to 27.6 C/g for poly(NIPAM)-acrylate shell microgels P(NIPAM-AAS). After the addition of the acrylate monomer the mixture was refluxed for 4 h in N2 atmosphere, and subsequently, the microgels were filtered and dialyzed against distilled water for 2 days. Finally, the microgels were collected, freeze-dried, and stored at room temperature. Iron oxide nanoparticles were prepared by the coprecipitation method32 in the presence of the previously synthesized microgels. In a typical experiment, 0.1 g of P(NIPAM-AAS) microgels were dispersed in 50 mL of NaOH (0.1 M) aqueous solution. Afterward, 50 mL of a HCl solution (0.1 M) in which had been previously dissolved 32.5 mg (0.18 mmol) of FeCl3‚6H2O and 12 mg (0.09 mmol) of FeCl2‚4H2O (FeII/FeIII molar ratio ) 0.5) was slowly added dropwise to the microgel dispersion under continuous stirring at 25 °C. At the end of this process the milky microgel dispersion turned to red-orange, indicating iron oxide formation. The thermogravimetry analysis (TGA) reveled that the inorganic material incorporated after the synthesis was ca. 18% (w/w); this class of microgels is termed Fe18P(NIPAM-ASS). By keeping the same synthesis conditions but increasing the iron ion concentration by a factor of 2, microgels with 38% (w/w) of inorganic counterpart were obtained; this class of microgels is termed Fe38P(NIPAM-ASS). As result of the iron oxide incorporation, the negative charge of the microgels is reduced from 27.6 to 0.6 C/g and 0.4 C/g for Fe18P(NIPAM-ASS) and Fe38P(NIPAM-ASS), respectively, reducing considerably the aqueous stability of the synthesized material. With the aim of increasing the colloidal stability and reducing the particle agglomeration, we added 20 mg of sodium poly(styrene-sulfonate) (PSS) to the previously prepared magnetic microgels. The mixture was stirred during 48 h at room temperature, and afterward the dispersion was three times
centrifuged, decanted, and redispersed in distillated water. After the PSS adsorption, the superficial charged increased to 49.5 and 49.1 C/g for Fe18P(NIPAM-ASS) and Fe38P(NIPAM-ASS), respectively. The increment of the superficial charge permitted increasing the colloidal stability, which was investigated by means of velocity sedimentation analysis. The results, 0.81 and 1.1 µm‚s-1 for Fe18P(NIPAM-ASS) and Fe38P(NIPAM-ASS), respectively, indicated the high colloidal stability of the final magnetic microgels in aqueous solution. We noticed a small increase in the sedimentation velocity of the microgels with higher inorganic content, which was attributed to the increment of its density. Figure 1 shows SEM micrographs of the prepared microgels in the dried state. In Figure 1 one can observe significant differences in the microgel mean size for the three microgels synthesized. The mean hydrodynamic diameter of the microgels in the swollen state was measured by DLS, and the results are shown in the insets of Figure 1. The mean particle diameter was found to be 740 ( 60 nm for PNIPAM, 650 ( 85 nm for P(NIPAM-AAS), 550 ( 90 for Fe18P(NIPAM-ASS), and 440 ( 90 nm for Fe38P(NIPAM-ASS) microgels. The tendency of these values is consistent with the diameters obtained with SEM in the collapsed state (530 nm for P(NIPAM), 330 nm for P(NIPAM-AA), 210 nm for Fe18P(NIPAM-ASS), and 187 nm for Fe38P(NIPAM-ASS) The size reduction observed in P(NIPAM-AAS) microgels as compared to that in the neat P(NIPAM) microgels can be explained through the mechanism of microgel formation. Pelton et al.31 described this mechanism as a nucleation process of colloidal unstable nanogels, which are formed during the polymerization reaction. Due to their inherent instability, the precursor nanogels coagulate, forming a stable colloidal particle, which results in the final microgel.29 However, the presence of
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stabilizers such as emulsifiers or charged monomers increases the stability of the precursor particles, thus reducing the coagulation process and resulting in smaller microgels.30,31 The subsequent precipitation of the iron oxide on the preformed P(NIPAM-AAS) microgels leads to a further size reduction. Even though the exact mechanism for this size reduction is presently unclear, a possible explanation might be the combined effect of decreasing superficial charge and increasing the crosslink density of the microgels due to the presence of iron oxides. In fact, the reduction of the particle superficial charge, measured after incorporating the iron oxides, renders a more hydrophobic composite. Additionally, it has been shown in the past by Horkay et al.32 that incorporation of Ca+2 ions on polyacrylate hydrogels leads to the formation of coordination complexes between the carboxylic groups of the microgels and the ions that results in decreasing the degree of swelling, thus resulting in even smaller microgel sizes. A detailed TEM micrograph of Fe18P(NIPAM-AAS) microgels decorated with iron oxide nanoparticles is shown in Figure 2. TEM analysis carried out on these particles revealed that the magnetic nanoparticles, with average sizes of about 6.4 ( 2.6 nm, are mostly located on the outer part of the microgels. Selected area electron diffraction (SAED) patterns of the samples indicated that the nanoparticles are crystalline. The d-spacing can be calculated using the following modified Bragg equation:
Lλ ) dR where L is the distance between the sample and the detector (L ) 80 cm), λ is the wavelength of the electron beam at 200 kV (λ ) 0.025 Å), R is the radius of the diffraction rings. The results are shown in Table 1. All detected diffraction peaks are attributed to cubic γ-Fe2O3 phase or cubic Fe3O4 phase, indicating that the sample does not contain the rhombohedally canted hexagonal hematite R-Fe2O3 phase, or any iron hydroxides. Furthermore, the calculated lattice parameter from the SAED was found to be 8.350 ( 0.017 Å. Since the lattice parameter of maghemite (γ-Fe2O3) is 8.351 Å,34 and that of magnetite (Fe3O4) is 8.396 Å,35 the main crystalline phase of the synthesized nanoparticles inside the microgels can be identified as the cubic γ-Fe2O3 phase. These findings are supported also by X-ray diffraction (not shown here) which confirms that iron oxide is the cubic γ-Fe2O3 phase. Due to their size and structure the composite microgels are expected to exhibit super paramagnetic behavior.36 Figure 3 shows a detailed TEM micrograph of the Fe38P(NIPAM-AAS). The TEM micrograph shows microgels with a higher iron concentration located preferentially on the outer part. The magnetic response of the composite microgels can be easily probed with the use of a magnet (Figure 4). Figure 4A shows the Fe18P(NIPAM-AAS) microgels dispersed in water. When a magnet of 0.24 T is approached close to the aqueous dispersion, the Fe18P(NIPAM-AAS) microgels move due to the magnetic field and form a film on the flask wall close to the magnet, as seen in Figure 4B. The necessary time for such aggregation varies with respect to the strength of the magnetic field (around 10 min in this experiment). In a more systematic manner the magnetic properties of the hybrid microgels were investigated using a superconducting quantum interference device (SQUID) Figure 5. In Figure 5 one can observe that the composite microgels exhibit a superparamagnetic behavior. It is worth pointing out the good saturation level of the hybrid material, which increased with higher nanoparticle content, 10 emu/g for Fe18P(NIPAM-
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AAS) and 20 emu/g Fe38P(NIPAM-AAS). It is also interesting to note that no clear saturation plateau is reached for the composite particles between -20 and 20 kOe, which was the range of our experiment. Similar behavior was recently reported by Dutta and co-workers.46 They explained this phenomenon as an enhancement of the surface magnetic moment of the nanoparticles. This enhancement could be produced by strong interactions between the inorganic material and capping agents, e.g., carboxylic groups of the microgels, such as was proposed by Suber and co-workers.47 Our SQUID results indicate that the iron oxide particles are firmly attached on the surface of the microgels. Since envisaged applications of the microgels lie in their use as thermosensitive drug delivery systems, it is of pivotal interest to investigate their thermal behavior. As can be seen in Figure 6, the microgels exhibit different swelling behavior. In fact, the incorporation of acrylic acid renders microgels that still exhibit a strong phase transition but at a higher temperature than the neat P(NIPAM) (36 and 33 °C, respectively). This effect has been related with the hydrophilic effect of the sodium acrylate incorporation. This monomer introduces ionic repulsions, which could hamper the aggregation of the NIPAM segments, shifting to higher temperature the volume phase transition as was previously reported by Krazt and co-workers.38-39 On the other hand, the incorporation of the magnetic nanoparticles on the microgels provokes an additional shift in the LCST of the microgels to 40 °C as well as a variation in the volume transition ratio. In order to rule out that this increment could be due to the presence of PSS on the microgels, we measured size vs temperature of Fe18P(NIPAM-AAS) microgels without PSS. The result (added as Supporting Information, Figure 1) shows that LCST in these microgels occurs around 40 °C, indicating that such an increment in the LCST is due to the presence of magnetic nanoparticles within the polymer. From a physical chemistry point of view, this result is not fully understood. Pich et al.43 explained this effect as the result of dominant nanoparticle-nanoparticle interactions, which makes more difficult the polymer aggregation during the LCST, requiring higher temperatures to collapse the matrix. Nevertheless, it is worth pointing out that the introduction of magnetic nanoparticles could additionally introduce steric hindrances inside the polymer matrix, which could hamper the aggregation of the hydrophobic polymer segments that takes place above LCST, resulting in a higher temperature required to overcome this barrier and thus collapsing the Fe18P(NIPAM-AAS) microgels. This assumption was put to test in the case of the Fe38P(NIPAM-AAS) microgels’ thermal behavior. A seen in Figure 6 the Fe38P(NIPAM-AAS) microgels did not exhibit any volume phase transition in the studied temperature range. This result clearly indicates there is a restriction of movement imposed by the presence of iron nanoparticles. Lo´pez-Cabarcos et al.40 obtained similar results after incorporating polypyrrol in PNIPAM microgels.
Conclusions In summary, a simple and facile chemical route to synthesize multifunctional smart gels is discussed in the present study. Magnetic iron oxide nanoparticles were incorporated on the surface of P(NIPAM-AAS) microgels, rendering materials which are both magnetically and thermally responsive. TEM and SAED confirmed the presence of cubic γ-Fe2O3 nanoparticles mostly on the surface of the microgels. SQUID experiments corroborated the results of SAED, showing that indeed the iron oxide nanoparticles are superparamagnetic, cubic maghemite γ-Fe2O3. The incorporation of 38%(w/w) of iron oxide blocked the LCST
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of the microgels, while the immobilization of 18% (w/w) of iron oxide on the microgels shifted their volume transition temperature from 36 to 40 °C, yielding a material that is potentially well suited as a carrier for controlled and targeted drug release.
(MAT2006-13646-C03-01) of the Spanish Science and Education Ministry and from the CAMUCM Program for “Consolidation of Research Groups”. We acknowledge the EU for financial support through the network of excellence NANOFUN-POLY.
Acknowledgment. J.R.-R. acknowledges the Ramo´n Areces Fundation for a post-doc fellowship to carry out this work. We thank Dr. Luis Baldonero for his assistance with TEM and SEM experiments. E.L.C. acknowledges financial support from DGI
Supporting Information Available: Figure 1 of size vs temperature of Fe18P(NIPAM-AAS) microgels without PSS. This material is available free of charge via the Internet at http://pubs.acs.org. LA7009594
