Langmuir 2007, 23, 395-398
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Temperature-Responsive Semipermeable Capsules Composed of Colloidal Microgel Spheres David B. Lawrence,† Tong Cai,‡,§ Zhibing Hu,‡ Manuel Marquez,@,#,⊥ and A. D. Dinsmore*,† Department of Physics, UniVersity of Massachusetts, Amherst, Massachusetts 01003, Department of Physics, UniVersity of North Texas, Denton, Texas 76203, INEST Group Postgraduate Program and Research Center, Philip Morris USA, Richmond, Virginia 23234, Harrington Department of Bioengineering, Arizona State UniVersity, Tempe, Arizona 85287, and NIST Center for Theoretical and Computational Nanosciences, Gaithersburg, Maryland 20899 ReceiVed September 12, 2006. In Final Form: NoVember 21, 2006 We present semipermeable, hollow capsules (colloidosomes) that expand and contract upon heating and cooling. The capsules are composed of micrometer-sized poly(N-isopropylacrylamide)-co-acrylic acid microgel particles, which exhibit a reversible size transition near 34 °C. The microgel particles assemble on the surfaces of water droplets in oil. Addition of the diblock copolymer poly(butadiene-b-N-methyl 4-vinyl pyridinium iodide) to the oil results in soft, elastic membranes of microgel particles that remain intact after the droplet interfaces are dissolved. Under heating, the capsules contract reversibly by 13% or irreversibly by 40% in radius. These stimulus-responsive colloidosomes might be useful for controlled release or as microscopic actuators.
Introduction The self-assembly of particles at liquid-liquid interfaces has been shown to be a useful and flexible approach to forming materials for encapsulation.1-18 For example, forming a layer of micro- or nanoscopic particles around a liquid droplet can lead to hollow capsules (colloidosomes)4 in which interstices between the particles serve as pores with a controlled size. The membrane pore size (and hence permeability) depend upon the particle size. Moreover, colloidosomes can be self-assembled in large quantity from a variety of colloidal materials and might therefore find application in industry.19 Another advantage of the template approach to making materials, however, is the freedom to tune the composition of the micro or nanoparticles to incorporate new †
University of Massachusetts. University of North Texas. § INEST Group Postgraduate Program, Philip Morris USA. @ Research Center, Philip Morris USA. ⊥ Arizona State University. # NIST Center for Theoretical and Computational Nanosciences. ‡
(1) Velev, O. D.; Furusawa, K.; Nagayama, K. Langmuir 1996, 12, 2374. (2) Velev, O. D.; Furusawa, K.; Nagayama, K. Langmuir 1996, 12, 2385. (3) Velev, O. D.; Nagayama, K. Langmuir 1997, 13, 1856. (4) Dinsmore, A. D.; Hsu, M. F.; Nikolaides, M. G.; Marquez, M.; Bausch, A. R.; Weitz, D. A. Science 2002, 298, 1006. (5) Lin, Y.; Skaff, H.; Emrick, T. S.; Dinsmore, A. D.; Russell, T. P. Science 2003, 299, 226. (6) Lin, Y.; Skaff, H.; Bo¨ker, A.; Dinsmore, A. D.; Emrick, T.; Russell, T. P. J. Am. Chem. Soc. 2003, 125, 12690. (7) Cha, J. N.; Birkedal, H.; Euliss, L. E.; Bartl, M. H.; Wong, M. S.; Deming, T. J.; Stucky, G. D. J. Am. Chem. Soc. 2003, 125, 8285. (8) Croll, L. M.; Stover, H. D. H. Langmuir 2003, 19, 5918. (9) Wang, H.; Hobbie, E. K. Langmuir 2003, 19, 3091. (10) Cayre, O. J.; Noble, P. F.; Paunov, V. N. J. Mater. Chem. 2004, 14, 3351. (11) Noble, P. F.; Cayre, O. J.; Alargova, R. G.; Velev, O. D.; Paunov, V. N. J. Am. Chem. Soc. 2004, 126, 8092. (12) Cao, A. M.; Hu, J. S.; Liang, H. P.; Wan, L. J. Angew. Chem., Int. Ed. 2005, 44, 4391. (13) Duan, H. W.; Wang, D. Y.; Sobal, N. S.; Giersig, M.; Kurth, D. G.; Mohwald, H. Nano Lett. 2005, 5, 949. (14) Im, S. H.; Jeong, U. Y.; Xia, Y. N. Nat. Mater. 2005, 4, 671. (15) Panhuis, M. I. H.; Paunov, V. N. Chem. Commun. 2005, 1726. (16) Subramaniam, A. B.; Abkarian, M.; Stone, H. A. Nat. Mater. 2005, 4, 553. (17) Zeng, C.; Bissig, H.; Dinsmore, A. D. Solid State Commun. 2006, 139, 547. (18) Ngai, T.; Auweter, H.; Behrens, S. H. Macromolecules 2006, 39, 8171. (19) Gouin, S. Trends Food Sci. Technol. 2004, 15, 330.
properties into the colloidosome, such as sensitivity to magnetic fields13,20,21 or, potentially, to temperature, pH, or light intensity or frequency. Polymer-based microgel particles in particular offer a number of opportunities. Poly(N-isopropylacrylamide) (PNIPAm) microgels have attracted considerable recent interest because they exhibit a pH-, temperature-, or light-induced volume transition,22-26 thereby creating the potential for controllable properties.27-29 Below the lower critical solution temperature (LCST) of ∼34 °C, the microgel particles are swollen with water, but at higher temperatures, the polymer deswells and the particles shrink. PNIPAm microgel particles can also be synthesized with low size polydispersity and have been used as model colloids for the study of phase transitions.30-34 Here we show that colloidosomes composed of PNIPAmco-acrylic acid microgel particles retain the temperature sensitivity of the particles and expand and contract in a controllable way. In our fabrication process, the anionic microgel particles stabilized droplets of an aqueous phase in 2-octanol18,35 and were subsequently locked together by the addition of the diblock copolymer poly(butadiene-b-N-methyl 4-vinyl pyridinium iodide) to the octanol. Following dissolution of the droplet interface and (20) Duan, H.; Wang, D.; Kurth, D. G.; Mohwald, H. Ang. Chem., Int. Ed. 2004, 43, 5639. (21) Koo, H. Y.; Chang, S. T.; Choi, W. S.; Park, J. H.; Kim, D. Y.; Velev, O. D. Chem. Mater. 2006, 18, 3308. (22) Hirotsu, S.; Hirokawa, Y.; Tanaka, T. J. Chem. Phys. 1987, 87, 1392. (23) Siegel, R. A.; Firestone, B. A. Macromolecules 1988, 21, 3254. (24) Suzuki, A.; Tanaka, T. Nature 1990, 346, 345. (25) Saunders, B. R.; Vincent, B. AdV. Colloid Interface Sci. 1999, 80, 1. (26) Garcia, A.; Marquez, M.; Cai, T.; Rosario, R.; Hu, Z.; Gust, D.; Hayes, M.; Vail, S. A.; Park, C.-D. Langmuir published online Oct 19, http://dx.doi.org/ 10.1021/la061632n. (27) Reese, C. E.; Mikhonin, A. V.; Kamenjicki, M.; Tikhonov, A.; Asher, S. A. J. Am. Chem. Soc. 2004, 126, 1493. (28) Huang, G.; Gao, J.; Hu, Z. B.; John, J. V. S.; Ponder, B. C.; Moro, D. J. Controlled Release 2004, 94, 303. (29) Nayak, S.; Lyon, L. A. Angew. Chem., Int. Ed. 2005, 44, 7686. (30) Senff, H.; Richtering, W. Langmuir 1999, 15, 102. (31) Wu, J. Z.; Zhou, B.; Hu, Z. B. Phys. ReV. Lett. 2003, 90, 048304. (32) Tang, S. J.; Hu, Z. B.; Cheng, Z. D.; Wu, J. Z. Langmuir 2004, 20, 8858. (33) Stieger, M.; Pedersen, J. S.; Lindner, P.; Richtering, W. Langmuir 2004, 20, 7283. (34) Alsayed, A. M.; Islam, M. F.; Zhang, J.; Collings, P. J.; Yodh, A. G. Science 2005, 309, 1207. (35) Ngai, T.; Behrens, S. H.; Auweter, H. Chem. Commun. 2005, 331.
10.1021/la062676z CCC: $37.00 © 2007 American Chemical Society Published on Web 12/09/2006
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Figure 1. Confocal fluorescence microscope images of colloidosomes composed of 540-nm-radius PNIPAmco-AA microgel particles. (a, b) Three-dimensional projection of several colloidosomes with 95% water and 5% ethanol throughout. (c) A slice through the center of the colloidosomes shown in b. The scale bars are 5 µm.
transfer into aqueous solution, the colloidosomes were stable (Figure 1). They also expanded and contracted with heating and cooling. Experimental Section Microgel Particles. Poly(N-isopropylacrylamide) (PNIPAm)-coacrylic acid microgels were prepared by precipitation polymerization.36 NIPAm monomer (3.8 g, 33.6 mmol), acrylic acid (AA) (0.48 g, 6.7 mmol, 20 mol % NIPAm monomer), polyfluor 570 (methacryloexethyl thiocarbonyl rhodamine B, 1 mg), sodium dodecyl sulfate (0.01 g), and N,N′-methylene-bis(acrylamide) (0.067 g, 0.44 mmol, 1.3 mol % NIPAm monomer) in water (240 mL) at room temperature were purged with nitrogen and stirred at 400 rpm for 30 min and then heated to 60 °C. Potassium persulfate (0.166 g) in 10 mL of water was added to the reactor to initialize polymerization. The reaction was maintained at 70 °C under nitrogen for 4 h. After being cooled to room temperature, the resultant microgel particles were dialyzed for 1 week to remove surfactant and unreacted molecules. The dialysis water was changed three times every day. The cutoff molecular weight of the dialysis membrane was 13 000 Da. After dialysis, PNIPAm-co-AA microgels were concentrated by ultracentrifugation at 10 000 rpm for 1 h and redispersed in deionized water. The average hydrodynamic radius (Rh) and the radius distribution function of the PNIPAm-co-AA particles were characterized using a laser light scattering spectrometer (ALV Co. Germany). The dynamic light scattering experiments were performed at a scattering angle of θ ) 60° and a wavelength of 628 nm. The microgel particles were narrowly distributed with an Rh of about 540 nm and a polydispersity index of about 1.05. (The reverse emulsion technique could also lead to PNIPAM-co-AA particles with low polydispersity and with other materials incorporated.37) The inset of Figure 2 shows the average Rh as a function of temperature on heating the PNIPAm-co-AA microgel particles in deionized water at pH 7. The polymer concentration of the suspension is about 2 × 10-5 g/mL. Colloidosomes. Colloidosomes were produced using water droplets in oil as a template for the assembly of 540-nm-radius PNIPAm-co-AA microgel particles.4 The basic procedure, shown in Scheme 1, was to add a portion of the aqueous suspension of the PNIPAm-co-AA microgel particles to a larger volume of oil (here, 2-octanol) and then gently shake by hand for 10-15 s. During this process, droplets were formed and stabilized by the adsorption of the PNIPAm-co-AA particles to their surfaces. In detail, Milliporefiltered water was used to dilute the prepared 5 wt % PNIPAmco-AA microgel suspension to 1 wt %. A volume of 200 µL of this suspension was added to 5-10 mL of the 2-octanol (97+% purity, used as received from Sigma-Aldrich, St. Louis, MO). As reported (36) Pelton, R. H.; Chibante, P. Colloids Surf. 1986, 20, 247. (37) Yang, J.; Hu, D.; Fang, Y.; Bai, C.; Wang, H. Chem. Mater. 2006, 18, 4902.
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Figure 2. Radius (R) of PNIPAm-co-AA colloidosomes as a function of their temperature T. The radii are normalized by the value near 25 °C (T0). Square symbols represent the average of three colloidosomes. The open triangles correspond to the colloidosomes of Figure 3 and Table 1. The images show a colloidosome at 27.5 and at 51 °C. (Lower inset): Average hydrodynamic radius (Rh) of PNIPAm-co-AA microgel particles in suspension (not colloidosomes) as a function of temperature. The right-hand axis gives the radii normalized by the radius at 22 °C. earlier, this led to droplets that were stabilized by a layer of PNIPAmco-AA particles.18,35 We found, however, that the PNIPAm-co-AA layer fell apart after the droplet interfaces were dissolved in ethanol. Therefore, to tie the PNIPAm-co-AA particles together we first added to the 2-octanol the amphiphilic diblock copolymer poly(butadiene-b-N-methyl 4-vinyl pyridinium iodide) (Polymer Source Inc., Montreal, Canada; cat. no. P1521-Bd4VPQ, used as received). The molecular weights of the polymer were 120 and 28.2 kDa for the butadiene and pyridinium iodide blocks, respectively. After 0.1 g of the diblock copolymer was mixed with 40 mL of 2-octanol, some undissolved sediment was discarded. Typically, a mixture consisting of 25 parts of the resultant 2-octanol solution and 1 part of the aqueous particle suspension was shaken by hand for 10-15 s, after which the solution was set aside for 48 h. A lengthy delay time was found to be necessary to achieve robust capsules. The excess 2-octanol was then removed from the top of the solution with a pipet, leaving only the settled, coated water droplets in a small amount of 2-octanol. Ethanol (190 proof, 15 mL) was added to the solution, dissolving the droplet interfaces (i.e., the template). The ethanol-wash step was repeated. After they settled to the bottom of the vial, the colloidosomes were transferred by pipet into water to obtain a suspension in 95 vol % water and 5 vol % ethanol. Imaging and Heating. The structure and temperature response of PNIPAm-co-AA colloidosomes were investigated using brightfield and fluorescence confocal optical microscopy (VT-Eye from VisiTech International, Sunderland, U.K.) during controlled heating. The variation of colloidosome size with temperature was measured by heating the samples on the stage of an inverted microscope. Experiments were performed with one of two heating methods: an objective heater (Carl Zeiss MicroImaging, Inc., Thornwood, NY) from below or a resistively heated (Warner Instruments, Hamden, CT) sapphire plate from above. Our procedure was to increase the heating power in discrete steps (with a typical heating rate of ∼1 °C/min), allowing the temperature to stabilize each time before images were recorded. The temperature, T, was measured with a thermocouple placed into contact with the sample slide. The change in temperature throughout each experiment was well known, but there may have been a systematic offset of a few degrees.
Results and Discussion Fluorescence confocal microscopy showed that these shells were stable, permeable to fluorescein dye (discussed below), and hollow. The image of Figure 1c shows a thin slice through the equatorial plane of a capsule, clearly showing the ring of
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Langmuir, Vol. 23, No. 2, 2007 397 Scheme 1. Formation of Capsules Composed of PNIPAm Microgel Spheres
fluorescent microgel particles and the hollow (solvent-filled) interior. The mechanical rigidity of the colloidosomes required the presence of the diblock copolymer. We speculate that the diblock copolymer’s pyridinium iodide block, which is hydrophilic and cationic in water, binds electrostatically to the PNIPAmco-AA particles at near-neutral pH. Previous electrophoretic mobility measurements show that PNIPAm-co-AA microgel particles are anionic.33,38 For further evidence of the anionic charge of these PNIPAm-co-AA microgel particles, we exposed part of a glass substrate to an aqueous solution of poly-L-lysine, thereby creating a cationic surface.39 We found that the PNIPAmco-AA microgel particles adsorbed at high concentration on the regions of the glass that had been exposed to poly-L-lysine but not elsewhere on the glass surface. As additional support, a previous study of the same diblock copolymer concluded that the cationic N-methyl 4-vinyl pyridinium iodide block complexes with anionic DNA at the interface between water and toluene.40 Response to Heating. We investigated four separately produced samples. In every case as samples of PNIPAm-co-AA colloidosomes were heated, their radius decreased. Figure 2 displays the average radius of the colloidosomes as a function of T. The plot shows a monotonic decrease in the radius, with a maximum shrinkage of approximately 40% at T ≈ 64 °C. This change in size without breakage indicates the colloidosome’s permeability to aqueous solution. Additionally, experiments were performed with colloidosomes immersed in water to which fluorescein dye was added. Confocal microscope images show that the fluorescein molecules permeate these colloidosomes. Control experiments using solid spheres showed dark interiors, demonstrating that the confocal microscope has sufficient resolution to isolate fluorescence from the interior region. The average hydrodynamic radius of the constituent PNIPAmco-AA particles in solution (i.e., before being formed into colloidosomes) is shown in the lower inset of Figure 2. Although the trend is the same, the precise scaling of the capsule’s R(T) is not identical to that of the bare microgel particles. When T < 52 °C, the capsules and the bare particles shrank in size by comparable fractions, though there might be a temperature offset attributable either to a systematic error in T or to the presence of 5 wt % ethanol in the capsule solution. At higher temperatures, however, the colloidosomes appear to have shrunk substantially more. In general, the colloidosomes show a broader temperature transition range than the PNIPAM-co-AA microgels. This may be due to the addition of amphiphilic diblock copolymer as a crosslinker. Reversibility. The colloidosome size change was reversible for modest temperature changes, 28.0 °C < T < 42.5 °C. To study reversibility, we heated a PNIPAm-co-AA colloidosome to 42.5 °C and then measured its radius by analysis of a brightfieldoptical-microscope image. Then the sample was cooled to 28 °C, and the radius was again measured. This process was repeated, (38) Gilanyi, T.; Varga, I.; Meszaros, R.; Filipcsei, G.; Zrinyi, M. Phys. Chem. Chem. Phys. 2000, 2, 1973. (39) Mazia, D.; Schatten, G.; Sale, W. J. Cell Biol. 1975, 66, 198. (40) Korobko, A. V.; Jesse, W.; van der Maarel, J. R. C. Langmuir 2005, 21, 34.
Table 1. Temperature (T) and Radius (R) of a PNIPAm Colloidosome That Was Heated and Cooled Several Times in Succession and Underwent a Reversible 13% Size Changea cycle 1 2 3 4 5 6 7 8 9 10 11 12 no. T (°C) 28.0 42.5 28.0 42.5 28.0 42.5 28.0 42.5 28.0 42.5 28.0 42.5 ((0.1) R (µm) 4.8 4.1 4.8 4.2 4.8 4.3 4.8 4.2 4.8 4.3 4.8 4.3 ((0.1) a The uncertainties in R arose from image analysis. These average radii are also shown as the ∆ symbols in Figure 2.
Figure 3. Optical microscope images of two PNIPAm-co-AA colloidosomes in a 95 vol %/5 vol % water/ethanol solution as they were heated resistively on a sapphire plate and subsequently cooled back to room temperature. (a) At room temperature, prior to heating. (b) As the temperature was increased from room temperature, the colloidosome continuously shrank. (c) At 64 °C, the colloidosome had shrunken to ∼60% of the radius in a. (d) After the same sample returned to room temperature, it did not reexpandsthe size change was irreversible. The black scale bars are 5 µm in length.
with R(T) recorded each time (Table 1). After five cycles, R(28 °C) was indistinguishable from what it had been prior to any heating. Similarly, there was no statistically significant change in R(42.5 °C). Qualitatively similar behavior was seen in other colloidosomes in this sample and in other samples. As shown in Figure 2 (∆), the average size change in this experiment agreed with results from separate samples that were heated just once. Experiments with a larger change in temperature revealed an irreversible size change. Figure 3 shows a pair of colloidosomes from the same batch as in the previous experiment, which were heated to ∼64 °C and then cooled to room temperature. Though the capsule monotonically shrank to 60% of its initial radius during heating, it did not expand on cooling. The two experiments reported here refer to colloidosomes from the same sample, effectively eliminating the possibility that some extraneous experimental detail caused the observed difference in reversibility. Experiments performed with colloidosomes produced in completely independent samples verified these results. We attribute the irreversibility of the size change to the increase in the van der Waals attraction and increasing overlap of PNIPAmco-AA particles at high T.33,38,41,42 We speculate that as the sample is cooled after a modest T increase the expanding polymer creates steric repulsion between neighboring particles. This steric repulsion must be sufficient to overcome the van der Waals attraction, which is fairly small because the particles retain a substantial amount of water and their dielectric constant is thus well matched to the aqueous solvent. In this regime, the heating (41) Snowden, M. J.; Marston, N. J.; Vincent, B. Colloid Polym. Sci. 1994, 272, 1273. (42) Saunders, B. R.; Vincent, B. Colloid Polym. Sci. 1997, 105, 11.
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and cooling are expected to cause a uniform change in the size of the capsule and of the pores within it. As the sample is cooled after a large T increase, however, the polymer still swells, but the resulting repulsion is not sufficient to overcome the van der Waals force between the cores of the microgel particles. At higher temperatures, earlier scattering and electron microscopy showed that the particles form a dense polymer core33,38,43 so that the dielectric constant is no longer closely matched to the solvent and the Hamaker constant increases. After the high-temperature heating, therefore, the heating/cooling cycle does not change the mean distance between particles. It might, however, lead to variation in the permeability of the interstices between cores owing to expansion and contraction of the surface regions of the microgel particles. Future work should also consider other explanations, such as an irreversible hydrophobic attraction or a rearrangement of the microgel particles in the shell.
Conclusions To summarize, temperature-responsive colloidosomes composed of PNIPAm-co-AA microgel particles were formed by self-assembly. Droplets of aqueous solution in 2-octanol formed templates, whereon the microgel particles assembled to reduce the total interfacial energy. The microgels were then electrostatically locked together by the diblock copolymer poly(butadieneb-N-methyl-4-vinyl pyridinium iodide), and the interface was washed away with ethanol. Following transfer into aqueous solution, the colloidosomes exhibited a significant reduction in overall size as the solution temperature was increased. The magnitude of the size change was comparable to that of the microgel particles in solution. The size change was reversible
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through small changes in T (to at least 42.5 °C, corresponding to a 13% radius reduction) but irreversible through larger temperature changes (e.g., 64 °C, corresponding to a 40% reduction in radius or ∼80% in volume). We attribute the irreversibility to the increased van der Waals attraction among the microgel particles in their collapsed state. Self-assembly of responsive particles at interfaces might lead to a number of interesting materials. Because the assembled structure maintains the properties of the constituent particles, there is considerable opportunity for additional stimuli such as light or pH. Capsules or membranes composed of PNIPAmco-AA or other responsive microgel particles might find use as microscopic pumps or actuators. They might also find use in controlled release applications because the colloidosomes formed here should exhibit a stimulus-responsive permeability owing to the change in pore size that accompanies a rescaling of the capsule size. Alternatively, colloidosomes might be formed with a mixture of swellable and nonswellable particles; a contraction of the former could create pores in the membrane or induce sufficient stress to rupture it. Moreover, the primary network of crosslinked polymer chains inside each PNIPAm-co-AA microgel particle44 provides the potential to entrap and release biomacromolecules.28 Acknowledgment. We thank Matthew Gratale, Jing Zhou, Xiaotao Peng, John Savage, and Paul Dubin for helpful discussions and technical assistance. We are also grateful to Philip Morris USA, Inc. for support through their INEST consortium and to the NSF-supported Materials Research Science and Engineering Center on Polymers (DME-0213695). Z.H. gratefully acknowledges the support from the National Science Foundation under grant no. DMR-0507208. LA062676Z
(43) Crassous, J. J.; Ballauff, M.; Drechsler, M.; Schmidt, J.; Talmon, Y. Langmuir 2006, 22, 2403.
(44) Hu, Z. B.; Lu, X. H.; Gao, J.; Wang, C. J. AdV. Mater. 2000, 12, 1173.
