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Stability and Mechanical Properties of Polyelectrolyte Capsules Obtained by Stepwise Assembly of Poly(styrenesulfonate sodium salt) and Poly(diallyldimethyl ammonium) Chloride onto Melamine Resin Particles Changyou Gao,†,‡ Stefano Leporatti,‡,§ Sergio Moya,‡ Edwin Donath,*,‡ and Helmuth Mo¨hwald‡ Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China, and Max-Planck Institute of Colloids and Interfaces, D-14424 Potsdam, Germany Received November 7, 2000. In Final Form: March 6, 2001 Capsules composed of poly(styrene sulfonate, sodium salt) (PSS)/poly(diallyldimethyl ammonium) chloride (PDADMAC) were prepared by layer-by-layer deposition of the polyelectrolytes on melamine formaldehyde colloidal templates followed by the decomposition of the cores by hydrochloride. A yield of more than 90% of intact capsules was achieved if (i) the core diameter was equal to or less than 3.8 µm and (ii) not more than five pairs of layers were adsorbed. When the cores were larger or the layers were thicker, the osmotic pressure difference caused by core dissolution led to an increased frequency of wall rupture. The elasticity modulus of a multilayer consisting of five pairs of PSS/PDADMAC was about 140 MPa as measured by osmotic pressure induced capsule deformation.
Introduction Nano- and micron-sized polyelectrolyte capsules are of both scientific and technological interest because of their potential applications as new colloidal structures in areas such as medicine, drug delivery, and catalysis.1-3 Biopolymers such as proteins, enzymes, or nucleic acids may be encapsulated, transported, and released afterward. Recently, novel nano- and micrometer-sized capsules have been prepared by stepwise adsorption of polyelectrolytes (PE)4-6 onto charged colloidal templates,7-9 followed by decomposition of the core.8-9 This fabrication technique allows control of the capsule size and shape, the capsule wall thickness, and the capsule wall composition. The structure and properties of the capsules can be designed to match various applications. Capsules with a * To whom correspondence should be addressed. Email:
[email protected]. † Zhejiang University. ‡ Max-Planck Institute of Colloids and Interfaces. § Present address: Digital Instruments/VEECO Metrology Group, Janderstrasse 9, D-68199 Mannheim, Germany. Email: leporatti@ digmbh.de. (1) Lewis, D. D. In Biodegradable Polymers and Drug Delivery Systems; Chasin, M., Langer, R., Eds.; Marcel Dekker: New York, 1990. (2) McGee, J. P.; Davis, S. S.; O’Hagan, D. T. J. Controlled Release 1995, 34, 77. (3) Price, James C. Diffusion controlled systems: Polymeric microcapsules. In Polymers for controlled drug delivery; Tarcha, P. J., Ed.; CRC Press: Boca Raton, FL, 1991; pp 1-14. (4) Decher, G. Science, 1997, 277, 1232. (5) Decher, G. In Templating, self-assembly and self-organisation; Sauvage, J.-P., Hosseini, M. W., Eds.; Pergamon: Oxford, U.K., 1996; Vol. 9, p 507. (6) Decher, G.; Hong, J. D.; Schmitt, J. Thin Solid Films 1992, 210/ 211, 831. (7) Keller, S. W.; Johnson, S. A.; Brigham, E. S.; Yonemoto, E. H.; Mallouck, T. E. J. Am. Chem. Soc. 1995, 117, 12879. (8) Donath, E.; Sukhorukov, G.; Caruso, F.; Davis, S.; Mo¨hwald, H. Angew. Chem., Int. Ed. 1998, 37, 2201. Caruso, F.; Caruso, R. A.; Mo¨hwald, H. Science 1998, 281, 1111. (9) Caruso, F.; Trau, D.; Mo¨hwald, H.; Renneberg, R. Langmuir 2000, 16, 1485.
given size and a given number of polyelectrolyte layers including surfactants and nanoparticles and derived from different templates can be fabricated.9-11 So far, these capsules have been characterized by scanning force microscopy (SFM), confocal laser scanning microscopy (CLSM), fluorescence and UV-vis spectroscopy, electrophoresis, electrorotation, and single particle light scattering. Various properties of the capsules, such as the morphology both in the wet state and in the dry state, their stability upon annealing, the elasticity, the surface charge, the capacitance and wall conductance, as well as the permeability have been explored.12-20 It was shown that organic and inorganic materials can be precipitated inside capsules.20 Polymerization reactions were conducted to fabricate polymer-containing capsules.21 A solvent exchange protocol yielded capsules filled with nonpolar liquids.18 The typical hollow polyelectrolyte capsules produced so far were composed of alternating poly(styrenesulfonate (10) Moya, S.; Da¨hne, L.; Voigt, A.; Leporatti, S.; Donath, E.; Mo¨hwald, H. Colloids Surf., A, in press. (11) Antipov, A. A.; Sukhorukov, G. B.; Leporatti, S.; Radtchenko, I. L.; Donath, E.; Mo¨hwald, H. Colloids Surf., A, in press. (12) Sukhorukov, G. B.; Donath, E.; Davis, S. A.; Lichtenfeld, H.; Caruso, F.; Popov, V.; Mo¨hwald, H. Polym. Adv. Technol. 1998, 9, 759. (13) Sukhorukov, G. B.; Brumen, M.; Donath, E.; Mo¨hwald, H. J. Phys. Chem. B 1999, 31, 6434. (14) Sukhorukov, G. B.; Donath, E.; Lichtenfeld, H.; Knippel, E.; Knippel, M.; Budde, M.; Mo¨hwald, H. Colloids Surf., A 1998, 137, 253. (15) Leporatti, S.; Voigt, A.; Mitlo¨hner, R.; Sukhorukov, G.; Donath, E.; Mo¨hwald, H. Langmuir 2000, 16, 4059. (16) Gao, C. Y.; Leporatti, S.; Donath, E.; Mo¨hwald, H. J. Phys. Chem. B 2000, 104, 7144. (17) Gao, C. Y.; Donath, E.; Moya, S.; Dudnik, V.; Mo¨hwald, H. Eur. Phys. J. E, in press. (18) Moya, S.; Sukhorukov, G. B.; Auch, M.; Donath, E.; Mo¨hwald, H. J. Colloid Interface Sci. 1999, 216, 297. (19) Georgieva, R.; Moya, S.; Leporatti, S.; Reichle, C.; Neu, B.; Ba¨umler, H.; Donath, E.; Mo¨hwald, H. Langmuir 2000, 16, 7075. (20) Sukhorukov, G. B.; Da¨hne, L.; Hartmann, J.; Donath, E.; Mo¨hwald, H. Adv. Mater. 2000, 12, 112. (21) Da¨hne, L.; Leporatti, S.; Donath, E.; Mo¨hwald, H. J. Am. Chem. Soc., in press.
10.1021/la0015516 CCC: $20.00 © 2001 American Chemical Society Published on Web 05/03/2001
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sodium salt) (PSS) and poly(allylamine hydrochloride) (PAH). Nanoparticles, metal ions, biopolymers, lipids, and photochromic ionenes were also incorporated into polyelectrolyte capsules by substituting one or more polyelectrolyte layers with species of the same charge.9,22 Thus, composite capsules with special functionalities have been fabricated. When the positively charged poly(diallyldimethyl ammonium) chloride (PDADMAC) was used instead of PAH for preparation of capsules, problems were encountered with capsules breaking upon template removal as the result of swelling. Presumably, the osmotic pressure difference built up during core dissolution was too large for the capsule walls to withstand. It is not clear whether a smaller permeability compared with the PAH/PSS capsule resulting in a prolonged retention of the core degradation products inside is responsible for the failure of capsule production or whether the walls themselves are more fragile as a result of their different composition. To study these problems, at first conditions had to be found which ensured the fabrication of intact capsules consisting only of PDADMAC and PSS. Only then could their properties be studied and compared with those made from PSS and PAH. This paper thus reports the conditions at which PSS/PDADMAC capsules could be fabricated by the membrane filtration technique.23 The mechanical properties of PSS/PDADMAC capsules were then compared with those of PSS/PAH capsules. Their elasticity was indeed smaller. The different molecular structure of the polycation (PDADMAC) as compared with PAH is thought to be responsible for the differences in the mechanical properties. Materials and Methods Materials. The sources of chemicals were as follows: PSS, Mw ∼ 70 000, and PDADMAC, medium Mw ∼ 200-350 kD, 20 wt % in water, Aldrich; fluorescein isothiocyanate labeled albumin (FITC-albumin), FITC 12 mol/mol albumin, Sigma; weakly crosslinked melamine formaldehyde particles (MF particles), Microparticles GmbH, Germany. All chemicals were used as received. The water used in all experiments was prepared in a three-stage Milli-Q Plus 185 purification system and had a resistivity higher than 18.2 MΩ cm. Capsule Preparation. A membrane filtration technique was employed to consecutively adsorb PSS and PDADMAC onto MF particles.23 The adsorption of polyelectrolytes (1 mg/mL) was conducted in 0.5 M NaCl solution for 5 min followed by three washings in H2O. Then, the respective oppositely charged polyelectrolyte species was added. After the desired number of layers was assembled, the coated particles were treated in HCl solution (pH 1.1) to decompose the MF cores. The produced MF core degradation products and excess HCl were washed off until a neutral pH was established by filtration with gentle agitation. The outermost layer in this study is always the positively charged PDADMAC. FITC-Albumin-Labeled Capsules. Equal amounts of capsule suspension and FITC-albumin solution (1 mg/mL) were mixed together and stored for 2 h at 4 °C. The suspension was centrifuged at 1145g and washed three times in H2O to remove the excess FITC-albumin. Osmotic Pressure Induced Capsule Deformation. A solution of FITC-albumin-labeled capsules was mixed with an equal amount of PSS solution of different concentrations and incubated for 5 min. CLSM was employed to determine the number of invaginated capsules. More than 200 capsules were inspected at each PSS concentration. The content of the unbroken capsules was defined as the number of invaginated capsules (22) Radtchenko, I. L.; Sukhorukov, G. B.; Leporatti, S.; Khomutov, G. B.; Donath, E.; Mo¨hwald, H. J. Colloid Interface Sci. 2000, 230, 272. (23) Voigt, A.; Lichtenfeld, H.; Sukhorukov, G. B.; Zastrow, H.; Donath, E.; Ba¨umler, H.; Mo¨hwald, H. Ind. Eng. Chem. Res. 1999, 38, 4037.
Gao et al. divided by the total number of capsules. A critical PSS concentration was defined as the concentration necessary to induce the invagination of 50% of the unbroken capsules. Confocal Laser Scanning Microscopy. Confocal micrographs were taken with the Leica TCS NT (Leica, Germany), equipped with a 100× oil immersion objective with numerical aperture of 1.4. For the observation of capsule sizes and shapes, 6-carboxyfluorescein (6-CF) was used as a label to visualize the capsules (when PSS was present in the bulk, FITC-albumin was employed). The capsule solution and 6-CF were mixed directly on a glass cover slip. The images of capsules were acquired immediately. For the determination of capsule deformation in PSS solution, the samples were mounted with nail lacquer. This ensured that evaporation of water did not occur. The PSS concentration remained thus constant during the counting protocol. Scanning Force Microscopy. SFM images were recorded in air at room temperature (20-25 °C) using a Nanoscope III Multimode SFM (Digital Instruments Inc., Santa Barbara, CA). This microscope enables the performance of contact SFM, lateral force microscopy (friction), and tapping mode measurements. Silicon nitride (Si3N4) cantilevers with a force constant of 0.58 N/m (Digital Instruments) have been used for contact SFM. Silicon tips (Olympus and Nanotips, DI) with a resonance frequency of ∼300 kHz and a spring constant of ∼40 N/m have been utilized for tapping mode SFM imaging. The contact force between the tip and the sample was kept as low as possible (>10 nN), and images were acquired in constant force mode (height mode) at a scan rate of 0.5-1 Hz. The samples have been prepared by applying a drop of the capsule solution onto freshly cleaved mica. The SFM images were processed by using Nanoscope software. Osmotic Pressure. The osmotic pressure of PSS solutions was measured by vapor pressure reduction with a Vapor Pressure Osmometer, no. A0280, Knauer, Germany. A pressure-concentration calibration curve was obtained by measuring a series of PSS solutions.
Results and Discussion Preparation of Unbroken Capsules. PDADMAC was assembled together with other negatively charged polyelectrolytes on macroscopic substrates and colloidal cores by the layer-by-layer assembling technique.16 Yet when PDADMAC was used to fabricate capsules on MF cores by this technique, instead of sealed polyelectrolyte capsules a large amount of broken capsules was found after HCl (pH 1.1) was added to the dispersion. Large openings in the capsule wall as shown in Figure 1a were observed. Instead of spheres, capsules with the shape of almost hemispheres were obtained. Sometimes the capsules opened even before the cores were completely decomposed (Figure 1b). Adsorbing a larger number of layers prior to the core decomposition, that is, preparing capsules with thicker and hopefully more stable walls, did not improve the capsule stability. Large pores even visible in optical resolution were found (Figure 1c). To explore the event of capsule breaking in more detail, the process of MF core decomposition was followed directly under CLSM. The capsules started to swell in a fraction of a second after the acidic solution was added. This increase in diameter could be followed over several seconds. Then, the polyelectrolyte wall ruptured at a certain moment of time close to the completion of the core decomposition process. The rest of the MF core was in most cases released from the interior. Sometimes a large patch of the capsule wall was found separated from the main part of the capsule wall. Capsule swelling and breaking can be understood as a result of the osmotic pressure difference created by the dissolution of the core. During the MF core decomposition process, the MF polymers constituting the core are degraded to smaller soluble units by the low pH. The
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Figure 1. CLSM images of polyelectrolyte capsules prepared by layer-by-layer deposition of PSS and PDADMAC onto MF colloidal particles with a diameter of 5.5 µm followed by decomposition of the cores by HCl: (a and b) 8 layers, with remains of cores in (b), and (c) 16 layers. The broken capsules can be clearly identified.
Figure 2. (a) CLSM image in aqueous solution and (b) SFM image in the dry state to show the successful fabrication of intact (PSS/PDADMAC)5 capsules templated on soluble MF particles with a diameter of 3.8 µm. The capsule diameter is 5.5 µm, which is larger than that of the template. Capsules labeled with FITC-albumin also have a diameter of 5.5 µm.
concentration of these degradation products inside capsules becomes quite large. The generated osmotic pressure difference between the bulk and the capsule interior is equilibrated by a hydrostatic pressure difference, the latter being responsible for the capsule expansion. The extent and duration of the osmotically induced tension onto the capsule wall depends on the interplay between the speed of core dissolution and the permeation rate of the core decomposition products through the capsule walls. Naturally, a larger permeability would be favorable for releasing the tension. Also, smaller capsules should have a higher stability against rupture. Indeed, at a given pressure difference ∆p the tension in the wall, λ, becomes λ ) ∆pr/ 2, where r is the capsule radius. On the other hand, the halftime of the concentration decay is V/AP ) r/3P, where P is the wall permeability and V and A are capsule volume and surface area, respectively. Hence, it can be expected that capsules with smaller radii and otherwise the same wall properties should be more stable during the core dissolution process, for the following reasons: (i) because of Laplace’s law the tension is smaller and (ii) the core degradation product concentration in the interior should decrease faster as a result of the more advantageous ratio between capsule volume and surface. In smaller capsules, the relatively larger area per unit volume corresponds to a higher net efflux per unit volume. Hence, it should be advantageous to use smaller cores to fabricate capsules
with PDADMAC to overcome the stability problem occurring as a result of the induced pressure difference. Following these theoretical predictions, the diameter of the MF particles was reduced to 3.8 µm. As shown in Figure 2, intact hollow PSS/PDADMAC capsules could then be fabricated. Only a negligible percentage of broken capsules was found by CLSM and SFM observations. Most capsules appeared in aqueous solution as typical intact hollow spheres (Figure 2a) with an average diameter of 5.5 µm. This diameter increase is understood as a result of capsule swelling during preparation (from 3.8 to 5.5 µm). In the dry state, the capsules are collapsed (Figure 2b). The percentage of unbroken capsules detected by the osmotic pressure method (see below Figure 3) was above 90%. (An unbroken capsule is defined as osmotically responding in PSS, Mw 70 000. Only in this case a shrinking in PSS solution occurs.) Attempts to prepare PSS/PDADMAC capsules templated on MF particles larger than 5.6 µm in diameter were not successful, regardless of the capsule wall thickness. It was further advantageous to add small amounts of the particle solution into a large amount of HCl (pH 1.1) solution. This ensured constancy of the pH during core dissolution. Otherwise, core decomposition is slowed while the pH catalyzed polymerization still continues.24 The high yield of unbroken (24) Gao, C. Y.; Leporatti, S.; Moya, S.; Donath, E.; Mo¨hwald, H., unpublished.
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Figure 3. CLSM images of polyelectrolyte capsules consisting of 10 layers of PSS/PDADMAC as a function of the PSS (Mw 70 000) bulk concentration. The PSS concentrations represented as wt % are indicated in the insets. A higher magnification of the corresponding image in (c) is shown in the inset.
capsules obtained by optimizing the dissolving conditions and using smaller cores enabled us to investigate the mechanical properties of capsules fabricated from PDADMAC and PSS. Capsule Elasticity. Recently, we employed a theoretical model, based on continuum mechanics (eq 1), which describes the relationship between the critical pressure differences Pc at which an indentation of the capsules occurs, the elasticity modulus µ, the capsule wall thickness δ (assumed homogeneous), and the capsule radius R.17
Pc ) 4µ
2
(Rδ )
(1)
Varying δ and R, eq 1 was verified, and the elasticity modulus of PSS/PAH multilayers was found to be 500750 MPa, depending on the Mw of PAH. Figure 3 shows that unbroken capsules undergo a shape transition from spherical (Figure 3a) into a cup shape at a certain critical PSS concentration (Figure 3b). At a higher PSS concentration, the capsules shrink further (Figure 3c,d). More than one invagination can be detected. At a very high PSS concentration, the capsules lose most of their internal volume (Figure 3e). The capsules with a spherical shape in Figure 3e represent broken ones. They are easily distinguished by the absence of shrinking. In such capsules, PSS can equilibrate through sufficiently large pores. A typical sigmoidal shape of the curve is obtained when the ratio of deformed capsules is plotted versus PSS concentration (Figure 4). At lower polyelectrolyte concentrations, the osmotic pressure is not large enough to overcome the elastic restoring force of the capsule walls. Thus, capsules do not invaginate at low PSS concentrations. At large enough PSS concentrations, all capsules, except broken ones, were invaginated. A three tangent evaluation technique as described before17 is used to estimate the critical PSS concentration, at which the shape transition occurs. As can be seen from Figure 4, it
Figure 4. Percentage of deformed capsules as a function of the PSS concentration. Capsule parameters: 10 layers of PSS/ PDAMAC, radius 2.2 µm. The critical PSS concentration is indicated.
corresponds to 2.6 wt % PSS which yields Pc to 1.8 × 105 N m-2. The capsule radius, 2.2 µm, and the capsule wall thickness, 40 nm, are known from CLSM and SFM measurements, 140 MPa, which is considerably smaller than that of a PSS/PAH multilayer.17 (The PSS/PDADMAC capsules are very sensitive to the environmental conditions, e.g., temperature, salts, and even proteins. The capsule diameter decreased from 5.5 to 4.4 µm (CLSM results) after incubation in albumin solution.) The different elasticity and stability of PSS/PAH and PSS/PDAMAC capsules should be attributed to differences in their structure. This difference is certainly caused by the different molecular architecture and chemical properties of PDADMAC compared with PAH because the anion is identical. It can be assumed that PAH can adopt a configuration which facilitates maximum interaction with PSS. On the other hand, the more rigid cyclopentane rings in the PDADMAC backbone provide a more stiff structure of the PDADMAC molecule. The ammonium cations in PAH are connected to freely rotating methylene groups which provide the possibility
Properties of Polyelectrolyte Capsules
for adjustment of their position toward the negatively charged sulfonate groups. The ammonium cations in PDADMAC are, however, fixed in cyclopentane rings which have a limited possibility of changing their position. The nature and the environment of the ammonium cations is also different in PAH compared with PDADMAC. The ammonium cations in the PAH are close to the molecular surface, whereas in the case of PDADMAC two large methyl groups are attached to the ammonium cation. Considering the van der Waals radii of the groups, the distances of closest approach between the centers of charges in the PDADMAC/PSS and PAH/PSS complex are 0.50 and 0.37 nm, respectively.25 The larger distance of closest approach between the charges together with a limited flexibility of PDADMAC should result in, on average, a weaker bond strength between the oppositely charged polyelectrolyte polymer chains compared with the interaction of PAH and PSS. The distribution of charges along the PDADMAC chain does not match that of PSS, because the repeat distances differ by more than 1 Å, whereas the distribution in PAH does. Another difference between PAH and PDADMAC is that in the case of PDADMAC the quaternary nitrogen charge cannot be removed by deprotonation like in the case of PAH. Therefore, the situation should be considered that during adsorption of PDADMAC a charged group without or together with a counterion may be transferred into a more hydrophobic environment which is certainly not advantageous. Altogether, it can be summarized that there are a number of factors which may lead to an overall weaker interaction of the PSS/PDADMAC complex com(25) DeMeijere, K.; Brezesinski, G.; Netz, R.; Joanny, J.-F.; Donath, E.; Mo¨hwald, H. Proc. Natl. Acad. Sci. U.S.A., submitted.
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pared with that of the PAH/PSS complex. This explains why the PDADMAC/PSS capsules are softer, because rearrangements in the complex are easier to accomplish. This is consistent with a lower elasticity, a larger degree of expansion during fabrication, and finally a smaller cohesion making the shells more susceptible to breakage. Whether the permeability properties are also changed remains to be investigated. Conclusion PSS/PDADMAC capsules derived from MF colloidal particles can be prepared with a yield of unbroken capsules higher than 90% by the layer-by-layer adsorption technique followed by decomposition of the templated MF cores by exposing the coated particles to pH 1.1 HCl solution. The elasticity modulus of the PSS/PDADMAC multilayer as obtained by the osmotic pressure method is 136 MPa, which is considerably smaller than that of the PSS/PAH multilayer. The apparent difference between the PSS/ PAH capsules and PSS/PDADMAC capsules with regard to their stability and elasticity is explained as the result of the different chemical nature of PAH and PDADMAC, which is responsible for an overall weaker interaction between PDADMAC and PSS compared with the PAH/ PSS interaction. This work has shown that by changing the chemical composition, capsules with largely different mechanical properties can be fabricated. They can be tailored by tuning the intermolecular interaction in the multilayer. Acknowledgment. C.Y.G. thanks the DAAD and the Max Planck Society for financial support. The work was partially supported by a grant from BMBF No. 03C0293A1. LA0015516
