Monodisperse Functional Colloidosomes with Tailored Nanoparticle

Mar 8, 2011 - Tobias Bollhorst , Tim Grieb , Andreas Rosenauer , Gerald Fuller .... Jonathan S. Sander , Randall M. Erb , Claude Denier , André R. St...
0 downloads 0 Views 2MB Size
Download PDF
ARTICLE pubs.acs.org/Langmuir

Monodisperse Functional Colloidosomes with Tailored Nanoparticle Shells J. S. Sander and A. R. Studart* Complex Materials, Department of Materials, ETH Zurich, 8093, Zurich, Switzerland.

bS Supporting Information ABSTRACT: We report the assembly of monodisperse colloidosomes containing a wide range of functional nanoparticles in the outer shell using a double emulsion templating method in a microfluidic device. By selecting nanoparticles of specific functionalities, hollow capsules with inert, magnetic, photocatalytic, and potentially biocompatible and piezoelectric shells are easily obtained. Proper control over the surface chemistry of the nanoparticles forming the shell and of the liquid interfaces involved is key to enable the assembly of colloidosomes using this double emulsification route.

’ INTRODUCTION Encapsulation and controlled release of materials are of great interest in biomedicine, food science, materials science, pharmaceutics, and agriculture.1-6 Illustrative examples are the protection of food flavor agents from moisture,3 the controlled release of drugs,2,4 and the release of reactive liquids in self-healing polymers.6 Containers for the encapsulant can be hydrogels, vesicles, porous particles, or hollow capsules. These carriers are usually tailored to the appropriate environment and releasetriggering mechanism. In general, the encapsulant is released by mechanical rupture or passive degradation of the shell material through abrupt or continuous dissolution. Degradation is often triggered by changes in pH, ionic strength, magnetic field, temperature, or concentration of reactive molecules.3,4,7-9 More sophisticated systems that allow for site-specific release have also been developed. This is of particular interest in cancer treatment, since it is desired that the highly aggressive drugs are liberated exclusively in affected regions. Examples of capsules developed to meet this goal include delivery vesicles functionalized with magnetic particles for guidance in magnetic fields or antibodies for specific detection of inflamed tissue.7,10 The development of capsules with an increasing number of functionalities is desired, since it should enhance our ability to manipulate and control their release behavior. Hollow capsules composed of colloidal particles in the shell, usually referred to as colloidosomes, can potentially display numerous functionalities.11-15 In principle, particles that form the shell can exhibit specific properties themselves or may be a convenient platform for the immobilization of molecular species of interest for site-specific recognition or controlled interactions. Conventional approaches for the formation of colloidosomes include, for example, the interfacial adsorption of particles on the surface of droplets in single emulsions.11-14,16-19 The drawbacks of this technique are the need for exchange of the liquid continuous phase after colloidosome formation and the low encapsulation efficiency. By contrast, colloidosomes fabricated in microfluidic devices using double emulsions as templates allow for high flexibility and efficient loading and capsule formation in a one-step process.20,21 Moreover, the controlled flow conditions r 2011 American Chemical Society

Figure 1. Schematic illustration of the double emulsion generation process in a double microcapillary device (top)20 and the formation of colloidosomes by solvent removal (bottom).21

achieved in microfluidic devices enable the preparation of highly monodisperse colloidosomes. In this method, nanoparticles with tailored wettability are confined in the middle phase of a double emulsion, while the encapsulant is sequestered in the inner phase (Figure 1). Since the middle phase has a finite solubility in the continuous phase, the nanoparticles are confined and eventually assembled into a stable shell upon removal of the middle fluid.21 Unlike colloidosomes produced by interfacial adsorption of particles in single Pickering emulsions,11-14,16-19 this approach leads to shells with multilayers of particles, increasing the capsule’s mechanical stability and enabling better control over the shell permeability. To date, colloidosomes templated with double emulsions have been limited to specially functionalized silica nanoparticles and polymeric particles.15,21 Here, we show that a wide range of materials can be used to form the shell of double-emulsion-templated Received: September 3, 2010 Revised: February 14, 2011 Published: March 08, 2011 3301

dx.doi.org/10.1021/la1035344 | Langmuir 2011, 27, 3301–3307

Langmuir colloidosomes by appropriately controlling the surface chemistry of both the nanoparticles and fluid interfaces. By extending the double emulsion technique to nanoparticles of other chemical compositions, we show that monodisperse capsules with functional shells of tailored chemical, magnetic, photocatalytic, and potentially piezoelectric properties can be obtained.

’ EXPERIMENTAL SECTION Materials. Al2O3 (average diameter d50 = 60 nm, density F = 3.6 g/ cm3, surface area A = 38 m2/g) was purchased from Nanophase Technology Inc. (Romeoville, IL); TiO2 (d50 = 21 nm, A = 50 m2/g, ca. 80% anatase and 20% rutile) was acquired from Evonik; SiO2 (d50 = 100 nm or 250 nm, F = 1.8 g/cm3, A = 2-6 m2/g) was purchased from Fiber Optic Center Inc. (New Bedford, MA). Poly(vinyl difluoride) (PVDF, d50 = 250 nm, F = 1.78 g/cm3) was purchased from Polyscience Inc. (Warrington, PA). Nanoclay platelets (Nanomer 1.30E, montmorillonite clay, d50= 8-10 μm, A = 14 m2/g) modified with 0.5-5 wt % aminopropyltriethoxysilane and 25-30 wt % octadecylamine were purchased from Sigma Aldrich Chemie GmbH (Germany). β-Tricalcium phosphate (TCP, d50 = 50 nm, A = 37 m2/g) was kindly supplied by Prof. Wendelin J. Stark (ETH Zurich).22 Fe3O4 nanoparticles were synthesized according to a modified version of the procedure described by Bilecka et al.23 Hydrophobization of the Fe3O4 particles was achieved during the synthesis by adding oleic acid while mixing the reactants (weight ratio of oleic acid to iron acetylacetonate of 2.7:1). Typically, Fe3O4 particles produced by this route exhibit a diameter between 5 and 15 nm. Fe3O4 particles with 10 nm size were also obtained from commercial ferrofluids (Ferrotec Co, Bedford, NH). Toluene (99.7%), butylamine, 2-propanol, trimethoxy(octadecyl)silane, polyethylene glycol sorbitan monolaurate (Tween 20), sorbitan trioleate (Span 85), poly(vinyl alcohol) (PVA, 87%-89% hydrolyzed, Mw = 31 000-51 000 g/mol), and fluorescein isocyanate dextran (Mw = 10 000 and 500 000 g/mol) were purchased from Sigma Aldrich Chemie GmbH. Oleic acid (>99.0%) and Rhodamine B were purchased from Fluka (Buchs, Switzerland). Silanization of SiO2 Nanoparticles. Silica particles (100 nm) were mixed with 20-30 wt % trimethoxy(octadecyl)silane and 2-3 wt % butylamine in 2-propanol. The mixture was sonicated for 10 min with an ultrasonic horn (Vibra cell VCX 130, Sonics) and stirred for 24 h. After stirring, the solution was centrifuged and resuspended in toluene three times to remove any excess silane and 2-propanol. Colloidosomes produced with silanized silica particles did not require the addition of surfactants into the middle oil phase, as specified in Table S1 of the Supporting Information. Microcapillary Device Fabrication. Borosilicate glass capillaries [inlet capillary, 1 mm outer diameter (o.d.), 0.2 mm inner diameter (i.d.), AIT Inc. New Fundland, NJ; collecting capillary, 1 mm o.d., 0.5 mm i.d., World Precision Instruments, Leipzig, Germany] were pulled using a Flaming/Brown micropipet puller (P-97, Sutter Instruments Co.). Dimensions of tapered tips were adjusted to 15-40 and 180-300 μm for the inlet and collecting capillaries, respectively, using a microforge (MF-830, Narishige). The inlet and collecting capillaries were aligned parallel within a square capillary (1.5 mm o.d., 1.05 mm i.d., AIT Inc. New Fundland, NJ) and fixed with a commercial fast curing epoxy glue (5 min Epoxy, ITW Devcon) keeping a separation distance of 80-110 μm between the tapered tips. Syringe tips (I and Peter Gonano, Breitenstein, Austria) were fixed at the ends of the square capillaries as inlets for the middle and the outermost phases and connected with polyethylene tubing (Scientific Commodities, Lake Havasu City, AZ) to glass syringes (Hamilton gastight, Reno, NV). Double Emulsification. Dripping was achieved using flow rates of 500-2000, 2000-10 000, and 8000-28 000 μL/h for the innermost,

ARTICLE

middle, and outermost fluids, respectively. The flow rates were controlled using programmable syringe pumps (PHD 2000, Harvard Apparatus GmbH, March-Hugstetten, Germany). Colloidal suspensions used as middle fluid are prepared by initially dispersing the nanoparticles in toluene with the help of an ultrasonic horn (10 min, Vibra cell VCX 130, Sonics). The nanoparticle concentrations reported are based on the mass of solvent where the particles were initially dispersed, whereas the concentrations of sorbitan trioleate (Span 85) are based on the mass of particles (Table S1 in the Supporting Information). PVA and Tween 20 concentrations were calculated with respect to the mass of water. Pictures of the double emulsification process were taken using a highspeed camera (Phantom V9.0, Vision Research, Wayne, NJ) connected to a Leica DM 6000 inverted microscope (Leica, Heerbrugg, Switzerland). Al2O3-Fe3O4 Composite Colloidosomes. To prepare magnetically responsive capsules, Fe3O4 was washed after the synthesis and dispersed in toluene, leading to a suspension with about 2.5 wt % magnetite. Meanwhile, an alumina suspension was prepared by dispersing 5 or 7.5 wt % 60 nm Al2O3 particles in toluene using 29 wt % sorbitan trioleate (Span 85). Equal volumes of the magnetite and alumina suspensions were mixed, resulting in final suspensions containing about 3.75 or 5 wt % nanoparticles. These oil-based suspensions were then used as middle phase to obtain Al2O3-Fe3O4 composite colloidosomes. Silanized SiO2-Fe3O4 Composite Colloidosomes. Silicamagnetite composite colloidosomes were produced using 100 nm silanized silica and a commercial ferrofluid (Ferrotec Co.). The ferrofluid was dried completely at 60 °C and resuspended in toluene. The suspension used as the middle oil phase for the preparation of the colloidosomes consisted of approximately 5 wt % silica and 2.5 wt % magnetite. β-TCP-Clay Composite Colloidosomes. To obtain TCPclay composite capsules, a 7.5 wt % suspension of clay particles in toluene was prepared and sonicated for 10 min using an ultrasonic horn (10 min, Vibra cell VCX 130, Sonics). This suspension was mixed with an equal volume of a 7.5 wt % suspension of TCP in toluene containing 15-40 wt % sorbitan trioleate (Span 85) as surfactant. This oil-based suspension was then used as middle phase to obtain TCP-clay composite colloidosomes. Pendant Drop Measurements. The interfacial tension of the oil-water interface was measured using the pendant drop method (PAT-1 Tensiometer, Sinterface Technologies, Berlin, Germany). All measurements were performed by forming a droplet of the oil in a continuous aqueous phase, except for the case of pure water in toluene. Typical concentrations of particles, sorbitan trioleate (Span 85), and PVA of 5.0-7.5, 12.5-15.0 (6-12 mM in the solvent), and 2 wt %, respectively, were used in these measurements. Data reported here were obtained after a constant interfacial tension had been reached, which usually occurred 100 to 300 s after droplet formation.

Adsorption and Photodegradation of Rhodamine B on Capsules. Rhodamine B was adsorbed on Al2O3 and TiO2 colloidosomes by immersing them in 1 mM solutions of the dye. After repeated washing in water, fluorescent microscopy images of the capsules were taken during irradiation with a strong UV-visible light source (320-400 nm, max power 120 W). Scanning Electron Microscopy (SEM). Samples were prepared for SEM by transferring the capsules to ethanol, drying them on a glass slide or a SEM sample holder, and finally sputtering them with platinum for 35 s at a current of 40 mA. Confocal Microscopy. Imaging of capsules by confocal microscopy was performed in a Zeiss LSM 510 confocal laser scanning system (Carl Zeiss, Oberkochen, Germany) using a 25 mW argon laser at an excitation wavelength of 488 nm. FITC dextran molecules were used as fluorescent dyes. 3302

dx.doi.org/10.1021/la1035344 |Langmuir 2011, 27, 3301–3307

Langmuir

ARTICLE

’ RESULTS AND DISCUSSION To obtain colloidosomes with specific functionalities, we used a variety of inorganic and organic nanoparticles to form the capsule’s shell. Al2O3 (60 nm) and SiO2 (100-250 nm) particles serve as examples of chemically inert nanoparticles that yield a mechanically stable platform for further functionalization of the capsule shell. Fe3O4 (5-15 nm), TiO2 (21 nm), and poly(vinyl difluoride) (PVDF) (250 nm) nanoparticles are used to obtain colloidosomes with magnetic, photocatalytic, and potentially piezoelectric functionalities, respectively. Finally, capsules composed of mixtures of β-tricalcium phosphate (TCP) and clay nanoparticles are produced to form composite shells that combine different properties, namely, biocompatibility and high surface area. To form double emulsions, an oil-based suspension loaded with the nanoparticles is used as the middle phase and two aqueous-based fluids are used as inner and outer phases. The stabilization of the two oil-water interfaces of the double emulsion is crucial to obtain monodisperse colloidosomes with nanoparticle shells of deliberate chemical compositions and properties. To investigate possible stabilizers for these interfaces, we measured the interfacial tension of the water-toluene interface in the presence of (i) sorbitan trioleate (Span 85), (ii) a mixture of free sorbitan trioleate and sorbitan-coated particles, and (iii) surface-active polyvinyl alcohol (PVA). The results show that the partially hydrolyzed PVA molecules markedly decrease the water-toluene interfacial tension (Table 1), reaching a value that is in line with those expected for other oilwater systems containing 2 wt % PVA in the aqueous phase.24 This indicates that the small fraction of nonhydrolyzed acetate groups in the PVA molecule (12%) makes it hydrophobic enough to adsorb at the water-toluene interface while the hydrophilic moieties are kept extended toward the aqueous phase.25-27 By contrast, a less pronounced reduction in the oil-water interfacial tension was observed in the presence of sorbitan trioleate (Table 1). Partially hydrolyzed PVA was therefore used to stabilize both the water-in-oil inner droplets and the oil-in-water outer droplets of the double emulsions. Later

experiments using PVA-free water as the inner aqueous phase showed that the sorbitan-coated nanoparticles present in the middle oil phase can also efficiently stabilize the water-in-oil inner droplets even in the absence of interfacially adsorbed PVA molecules. Since the interfacial tension of the bare toluenewater interface (34-36 mN/m) does not significantly decrease in the presence of sorbitan-coated particles (29-34 mN/m, Table 1), we conclude that the stabilization of the inner droplets in this case cannot be attributed to the adsorption of sorbitancoated particles or free sorbitan molecules at the toluene-water interface. Instead, the ability of colloidal particles to stabilize the inner water droplet of the double emulsions is probably related to jamming effects and structural forces arising upon thinning of the particle-loaded oil middle phase.28 Except for the prehydrophobized clay particles (discussed later), our interfacial tension data suggest that none of the bare and surface modified particles investigated here were surface-active (Table 1). In addition to stabilizing the water-oil interfaces, the preparation of colloidosomes from double emulsions requires loading of the middle oil phase with the colloidal particles that will later form the capsule shell. Due to their inherent hydrophilic nature, the oxide particles must be coated with a hydrophobic layer to facilitate their incorporation into the middle fluid (oil). Two surface modification approaches are used to hydrophobize the surface of the oxide particles. The silica nanoparticles (100 nm) are rendered hydrophobic via covalent attachment of alkyl silanes on their surface, whereas the other oxides are rendered hydrophobic by physically adsorbing sorbitan trioleate on their surfaces in toluene. Despite its weaker character, the physical adsorption of sorbitan trioleate resulted in significant coverage of the oxide particle surfaces. In the case of alumina, for example, the supernatant obtained after centrifugation of suspensions containing 12.5 wt % sorbitan trioleate shows the same interfacial tension against water as that of pure toluene, indicating that there is no free surfactant molecules in the continuous phase (Table 1). Once the conditions required for double emulsion stabilization and middle fluid dispersion were established, functional

Table 1. Interfacial Tension Data for the Toluene-Water Interface in the Presence of Different Surface-Active Speciesa interfacial tension (mN/m) Surfactants toluene/water

34-36

toluene/water þ2 wt % PVA toluene þ6 mM sorbitan trioleate/water

6 17 Surfactants þ Alumina Particles

suspension of alumina and sorbitan trioleate in toluene/water

31-34

supernatant of suspension of alumina and sorbitan trioleate in toluene/water

31

suspension of alumina and sorbitan trioleate in toluene/water þ2 wt % PVA

5

Surfactants þ Tricalcium Phosphate (TCP) Particles suspension of TCP and sorbitan trioleate in toluene/water

29

suspension of TCP and sorbitan trioleate in toluene/water þ2 wt % PVA

5

Hydrophobized Silica Particles suspension of hydrophobized silica in toluene/water suspension of hydrophobized silica in toluene/water þ2 wt % PVA

36 5

Hydrophobized Clay Particles suspension of 5 wt % hydrophobized clay in toluene/water a

6.0

The concentrations of alumina, silica, TCP, and clay particles used in these measurements were 7.5, 7.5, 7.5, and 5.0 wt %, respectively. 3303

dx.doi.org/10.1021/la1035344 |Langmuir 2011, 27, 3301–3307

Langmuir

ARTICLE

Figure 2. (A) Bright-field microscopy image of the double emulsification process in a microfluidic device. (B) Freshly formed double emulsions with 7.5 wt % Al2O3 in the toluene middle phase.

colloidosomes were prepared in glass double capillary microfluidic devices, as shown in Figure 2A,B.20 By forcing the inner and middle phases to coflow into a collecting capillary, single droplets of water can be formed under dripping mode in the continuous oil phase. The oil phase is in turn enveloped by another aqueous fluid that flows coaxially, but in the opposite direction with respect to the inner and middle fluids (Figures 1 and 2). If the capillaries are properly aligned and the flow rates are adjusted, monodisperse double emulsions are easily produced, as illustrated in Figure 2.20 The double emulsions prepared using these fluids are collected in excess water and left standing open in air for about 48 h. Since the toluene present in the middle phase is slightly soluble in water, it can be removed from the double emulsion by dissolving into the aqueous phase and eventually evaporating into open air. By removing the toluene, particles are confined and forced to assemble in the middle phase, ultimately leading to the formation of a stable shell. Colloidosomes with a thick shell of nanoparticles are successfully obtained, as shown in Figure 3. The mechanical strength of the resulting colloidosomes is sufficient to prevent their rupture during agitation and pipetting. This approach is applicable to many different materials. Capsules with shells consisting of Al2O3, SiO2, TiO2, Al2O3Fe3O4, and SiO2-Fe3O4 mixtures are successfully produced using PVA as stabilizer of the outer oil-in-water interface and the particles loaded in the middle phase as steric stabilizers of the water-in-oil inner droplets (Figure 3). The exact conditions used to obtain such colloidosomes are depicted in Table S1 (Supporting Information). Although the surface chemistry of oxides (Al2O3, SiO2, TiO2, and Al2O3-Fe3O4 mixtures) could be successfully changed using sorbitan trioleate, this molecule could not be used to completely hydrophobize the surface of β-tricalcium phosphate nanoparticles (β-TCP).22 As a result, the water-in-oil inner droplets of TCP-loaded double emulsions were not very stable. To circumvent this issue, we used commercially available prehydrophobized clay particles to adsorb at the water-in-oil inner droplets and thus stabilize the system. The adsorption of the prehydrophobized clay at the toluene-water interface was confirmed by pendant drop measurements, which revealed a reduction in interfacial tension from 34-36 to 6 mN/m upon addition of 5 wt % clay particles to the oil phase. The concept developed for hydrophilic particles was also extended to initially hydrophobic poly(vinyl difluoride) (PVDF) particles, leading to polymeric capsules with shells formed by a piezoelectric material (Figure 3 F). In this case, the hydrophobic particles can be directly suspended in toluene without further addition of surfactants. However, the absence of a surfactant steric layer on the PVDF particles made these suspensions more prone to agglomeration. This issue was circumvented by

Figure 3. Bright-field microscopy images of colloidosomes made from (A) Al2O3, (B) SiO2, (C) TiO2, (D) Al2O3-Fe3O4, (E) TCP-clay, and (F) PVDF particles in water.

magnetically stirring the suspension within the syringe to prevent sedimentation of the partly agglomerated PVDF particles during double emulsification. All polymeric and inorganic capsules produced by this route are stable in water for several months and can also be transferred into other solvents like ethanol and chloroform. In general, smaller particles lead to more stable colloidosomes, due to the stronger effect of van der Waals attractive forces between the particles in the shell. Yields higher than 80% were obtained for capsules containing Al2O3, SiO2, silanized SiO2-Fe3O4 (2:1 weight ratio), and TCP-clay (1:1 weight ratio) mixtures as shell nanoparticles. Lower yields were achieved for colloidosomes containing PVDF, TiO2 and Al2O3-Fe3O4 nanoparticles. In the case of PVDF, and to some extent TiO2, such lower yields can be attributed to the slightly agglomerated nature of these nanoparticles in the middle oil suspension, which favors particle sedimentation and fusion of the innermost droplet with the continuous aqueous phase. Except for the silanized SiO2-Fe3O4 capsules, the stabilization of systems containing Fe3O4 particles was more challenging, which is reflected in the lower yield obtained for the Al2O3-Fe3O4 colloidosomes. The monodisperse capsules obtained in this study exhibit diameters ranging from 100 to 200 μm, whereas the thicknesses of the capsule’s wall lie in the range 1-3 μm. The colloidosome diameter is 10-15% smaller than the size of the inner droplet of 3304

dx.doi.org/10.1021/la1035344 |Langmuir 2011, 27, 3301–3307

Langmuir

ARTICLE

Figure 4. SEM images of dry colloidosomes containing 100 nm silanized silica in the particle shell. (A) Colloidosome with relatively smooth silica surface obtained from double emulsions loaded with 7.5 wt % silica particles and exhibiting a thin middle oil layer. (B, C) Structure of the outer and inner surface of the colloidosome depicted in part A. (D) Colloidosome with extensively folded silica surface obtained from double emulsions loaded with 9.0 wt % silica particles and exhibiting a thick middle oil layer. (E) Detail of the folded structure of the outer surface of the colloidosome depicted in part D. (F) Cross section of the colloidosome shell, illustrating the formation of particle multilayers.

the double emulsion template. The pores within the capsule shell are formed by the interstices between the randomly packed nanoparticles. Pore sizes are estimated to be 10-15% of the particle size and thus range from 2 to 38 nm.13,21 The structure of the colloidosomes obtained is illustrated in Figure 4 for the case of shells consisting of 100 nm silanized silica particles. Colloidosomes made from double emulsions exhibiting a thin middle phase layer exhibited relatively smooth surfaces (Figure 4A,B), whereas those obtained from thick oil layers displayed folded surfaces (Figure 4D,E). Multiple folding is probably a result of the formation of a thin layer of precipitated PVA on the outer droplet surface that buckles due to shrinkage of the middle oil phase during removal of toluene. By decreasing the middle oil layer thickness and thus the extent of shrinkage during toluene removal, we were able to significantly reduce folding on the colloidosome surface, as shown in Figure 4A,B for the silanized SiO2 capsules. As opposed to the outer shell surface, the interior of the colloidosomes displayed densely packed particles with a very smooth texture (Figure 4C). The shell particles were observed to form highly packed multilayers, as illustrated in Figure 4F. Although the folding effect makes it difficult to obtain quantitative predictions, the shell thickness can be tuned by changing the concentration of particles and the thickness of the middle oil layer. Typically, high particle concentrations and thick oil layers resulted in colloidosomes with thicker particle shells. Similar structures and trends were obtained for colloidosomes made with other colloidal particles (Figure S1, Supporting Information). With the exception of the PVDF capsules, all colloidosomes exhibit a discontinuous film of PVA on the surface after drying. Such film does not prevent the permeation of molecules through the capsule. Using confocal microscopy, we confirmed that fluorescently labeled 10 000 g/mol dextran molecules can readily diffuse through the colloidosome shell. If needed, the PVA can

Figure 5. Functional colloidosomes with tailored nanoparticle shells. Normalized fluorescence intensity of Al2O3 and TiO2 colloidosomes coated with Rhodamine B as a function of time under UV light, including sequential images of both types of colloidosomes (capsule sizes 130 and 160 μm for Al2O3 and TiO2, respectively).

also be removed by heating the capsules in water at 60 °C for at most 12 h (Figure S1, Supporting Information). Our ability to tailor the nanoparticle shell composition using this route enables the preparation of monodisperse colloidosomes with functional properties. The use of the nanoparticle shell as an inert platform for the immobilization of other functional molecules is illustrated in Figure 5 using alumina nanoparticles in the capsule shell and rhodamine B as functional molecule. The charged surface of oxide nanoparticles allows for functionalization of the colloidosome with charged molecules through simple electrostatic interactions. 3305

dx.doi.org/10.1021/la1035344 |Langmuir 2011, 27, 3301–3307

Langmuir

ARTICLE

phase. This is illustrated in Figure 6C,D for the silanized SiO2Fe3O4 colloidosomes. Under rotating magnetic fields, these colloidosomes undergo controlled oscillatory motion (see video S2 in Supporting Information). To prove that no damage was caused to the shell during oil removal under a magnetic field, the Janus colloidosomes were immersed in a solution containing high molecular weight fluorescently labeled molecules (fluorescein isocyanate dextran, 500 000 g/mol, Sigma Aldrich). Confocal microscopy showed no fluorescence inside the capsules (see Supporting Information). While the fabrication of magnetically responsive colloidosomes has been previously demonstrated using silica particles of one particular size (10-20 nm),21 our approach allows for the preparation of both homogeneous and Janus magnetic capsules using particles of different sizes, shapes, and tailored chemical compositions.

Figure 6. (A) Motion of a Al2O3-Fe3O4 composite colloidosome in response to a magnetic field gradient. The position of the capsule 270, 540, and 810 ms after exposure to the field is indicated by faded images. Janus magnetic colloidosomes with magnetic particles (in black) predominantly positioned on one side of the capsule: (B) Al2O3-Fe3O4 colloidosomes obtained due to dewetting phenomenon during toluene removal and (C, D) silanized SiO2-Fe3O4 colloidosomes made by applying a magnetic field during removal of oil.

In another example, the presence of nanoparticles with intrinsic functional properties in the shell enables the preparation of colloidosomes displaying specific responses to external stimuli. We fabricated, for instance, TiO2 colloidosomes that can photocatalytically degrade rhodamine B on the capsule surface upon exposure to ultraviolet light (Figure 5).29 The loss of average intensity over the whole section of the colloidosome normalized by the initial intensity was taken here as a measure of the degradation of the dye. After 50 s of irradiation almost all the dye is degraded in the case of the TiO2 colloidosome, whereas a far slower degradation is observed on the Al2O3 colloidosome. Nonirradiated TiO2 did not show significant loss of intensity within several hours. Magnetically responsive colloidosomes were also produced using Al2O3-Fe3O4 and silanized SiO2-Fe3O4 mixtures as the nanoparticle shell. Figure 6A shows the movement of a Al2O3Fe3O4 magnetic colloidosome placed next to a magnet by overlaying several pictures taken with 270 ms time intervals (see also video S1 in the Supporting Information). Occasionally, dewetting of the oil phase at the final stages of drying30,31 and phase separation in such composite systems led to colloidosomes with an uneven distribution of particles in the shell. This phenomenon was exploited to fabricate Janus colloidosomes,32 as exemplified in Figure 6B for a magnetically active Al2O3Fe3O4 capsule containing magnetic nanoparticles positioned predominantly on one side of the capsule shell. The preparation of magnetic Janus colloidosomes at high yields was possible by placing a magnet on top of a vial loaded with wet colloidosomes. The magnet was kept at a distance of 1 cm from the colloidosomes until complete removal of the oil

’ CONCLUSIONS We show that monodisperse colloidosomes with functional nanoparticle shells can be prepared using a double emulsification technique in a microfluidic device by properly controlling the surface chemistry of interfaces and nanoparticles involved in the emulsification process. Stabilization of the outer and inner droplets of the double emulsion using a surface-active polymer and nanoparticles of tailored wettability, respectively, is crucial to obtain colloidosomes with various chemical compositions. The high mechanical stability, photoactivity, magnetic properties, potential biocompatibility, and high surface area of the colloidosomes prepared using this approach might enable further control over the transport and release behavior of capsules used in biomedicine, agriculture, food, pharmaceutics, and materials science. ’ ASSOCIATED CONTENT

bS

Supporting Information. Table S1, Figures S1 and S2, and Videos S1 and S2. This material is available free of charge via the Internet at http://pubs.acs.org.

’ AUTHOR INFORMATION Corresponding Author

*E-mail: [email protected].

’ ACKNOWLEDGMENT We thank the Swiss National Science Foundation for the financial support (grant number 200021_126646) and Prof. Dr. Wendelin Stark (ETH Zurich) for kindly providing the tricalcium phosphate nanoparticles used in this study. ’ REFERENCES (1) Tsuji, K. J. Microencapsulation 2001, 18 (2), 137–147. (2) Langer, R. Nature 1998, 392 (6679), 5–10. (3) Augustin, M. A.; Hemar, Y. Chem. Soc. Rev. 2009, 38 (4), 902–912. (4) Odonnell, P. B.; McGinity, J. W. Adv. Drug Delivery Rev. 1997, 28 (1), 25–42. (5) Park, J. K.; Chang, H. N. Biotechnol. Adv. 2000, 18 (4), 303–319. (6) White, S. R.; Sottos, N. R.; Geubelle, P. H.; Moore, J. S.; Kessler, M. R.; Sriram, S. R.; Brown, E. N.; Viswanathan, S. Nature 2001, 409 (6822), 794–797. 3306

dx.doi.org/10.1021/la1035344 |Langmuir 2011, 27, 3301–3307

Langmuir

ARTICLE

(7) Matsusaki, M.; Akashi, M. Expert Opin. Drug Delivery 2009, 6 (11), 1207–1217. (8) Johnston, A. P. R.; Cortez, C.; Angelatos, A. S.; Caruso, F. Curr. Opin. Colloid Interface Sci. 2006, 11 (4), 203–209. (9) Lai, C. Y.; Trewyn, B. G.; Jeftinija, D. M.; Jeftinija, K.; Xu, S.; Jeftinija, S.; Lin, V. S. Y. J. Am. Chem. Soc. 2003, 125 (15), 4451–4459. (10) Zhang, J.; Misra, R. D. K. Acta Biomater. 2007, 3, 838–850. (11) Cayre, O. J.; Noble, P. F.; Paunov, V. N. J. Mater. Chem. 2004, 14 (22), 3351–3355. (12) Velev, O. D.; Furusawa, K.; Nagayama, K. Langmuir 1996, 12 (10), 2374–2384. (13) Dinsmore, A. D.; Hsu, M. F.; Nikolaides, M. G.; Marquez, M.; Bausch, A. R.; Weitz, D. A. Science 2002, 298 (5595), 1006–1009. (14) Hsu, M. F.; Nikolaides, M. G.; Dinsmore, A. D.; Bausch, A. R.; Gordon, V. D.; Chen, X.; Hutchinson, J. W.; Weitz, D. A. Langmuir 2005, 21 (7), 2963–2970. (15) Miguel, A. S.; Scrimgeour, J.; Curtis, J. E.; Behrens, S. H. Soft Matter 2010, 6 (14), 3163–3166. (16) Akartuna, I.; Tervoort, E.; Studart, A. R.; Gauckler, L. J. Langmuir 2009, 25 (21), 12419–12424. (17) Duan, H. W.; Wang, D. Y.; Sobal, N. S.; Giersig, M.; Kurth, D. G.; Mohwald, H. Nano Lett 2005, 5 (5), 949–952. (18) Lin, Y.; Skaff, H.; Emrick, T.; Dinsmore, A. D.; Russell, T. P. Science 2003, 299 (5604), 226–229. (19) Wang, C. Y.; Liu, H. X.; Gao, Q. X.; Liu, X. X.; Tong, Z. ChemPhysChem 2007, 8 (8), 1157–1160. (20) Utada, A. S.; Lorenceau, E.; Link, D. R.; Kaplan, P. D.; Stone, H. A.; Weitz, D. A. Science 2005, 308 (5721), 537–541. (21) Lee, D.; Weitz, D. A. Adv. Mater. 2008, 20 (18), 3498. (22) Loher, S.; Stark, W. J.; Maciejewski, M.; Baiker, A.; Pratsinis, S. E.; Reichardt, D.; Maspero, F.; Krumeich, F.; Gunther, D. Chem. Mater. 2005, 17 (1), 36–42. (23) Bilecka, I.; Djerdj, I.; Niederberger, M. Chem. Commun. 2008, 7, 886–888. (24) Lankveld, J. M.; Lyklema, J. J. Colloid Interface Sci. 1972, 41 (3), 454–465. (25) Lyklema, J.; Vanvliet, T. Faraday Discuss. 1978, 65 (65), 25–32. (26) Buscall, R. Prog. Colloid Polym. Sci. 1978, 63, 15–26. (27) Bibette, J.; Leal-Calderon, F.; Schmitt, V.; Poulin, P., Emulsion science—Basic principles. An overview—Introduction. In Emulsion Science: Basic Principles—An Overview; Springer-Verlag Berlin: Berlin, 2002; Vol. 181, pp 1-4. (28) Ivanov, I. B.; Kralchevsky, P. A. Colloids Surf. A 1997, 128 (13), 155–175. (29) Wu, T. X.; Liu, G. M.; Zhao, J. C.; Hidaka, H.; Serpone, N. J. Phys. Chem. B 1998, 102 (30), 5845–5851. (30) Shum, H. C.; Lee, D.; Yoon, I.; Kodger, T.; Weitz, D. A. Langmuir 2008, 24 (15), 7651–7653. (31) Hayward, R. C.; Utada, A. S.; Dan, N.; Weitz, D. A. Langmuir 2006, 22 (10), 4457–4461. (32) Subramaniam, A. B.; Abkarian, M.; Stone, H. A. Nat. Mater. 2005, 4 (7), 553–556.

3307

dx.doi.org/10.1021/la1035344 |Langmuir 2011, 27, 3301–3307