From polymeric films to nanocapsules

Studies in Surface Science and Catalysis 132 Y. Iwasawa, N. Oyama and H. Kunieda (Editors) c 2001 Elsevier Science B.V. All rights reserved.

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From polymeric films to nanocapsules H. Mohwald, H. Lichtenfeld, S. Moya, A. Voigt, G. Sukhorukov, S. Leporatti, L. Dahne, A. Antipov, C. Y. Gao and E. Donath Max-Planck-Institute of Colloids and Interfaces, Am Muhlenberg 2, D-14476 Golm, Germany I. INTRODUCTION In recent years much has been learnt about the structure of organic films and interfaces, and techniques to prepare these films in a controlled way have been developed. These have concerned mostly planar systems, but there is no obvious reason why this knowledge could not be transferred to curved interfaces. This is most desirable in order to coat colloids for various reasons: One would be able to obtain systems with much specific surface area. This would allow not only many applications requiring controlled surfaces (e.g. chromatography, enzyme technology, separation technology), but also other techniques to study interfaces could be employed. Our motivation resulted fi-om the application of methods typically used for bulk samples: NMR, differential scanning calorimetry and flash spectroscopy. Coating colloids in a defined way is also a prerequisite to understanding colloidal solutions, because the interparticle interactions are determined by their interfaces. Having succeeded in coating colloids there is an obvious next step, to template colloids by dissolving the core and thus obtaining hollow capsules. This route will be proceeded in the following, demonstrating also the interesting properties and possible applications of these capsules. n. Preparation of coated Colloids and Capsules A technique to prepare polymeric films with nm precision has been introduced by Decher, and is called layer-by-layer adsorption /I/. With this technique a charged surface can be coated by dipping it into a solution of an oppositely charged polyelectrolyte. The latter is adsorbed reversing the surface charge under suitable conditions, and thus a polyelectrolyte with again the opposite charge can be adsorbed. Repeating the process leads to polymeric films of low roughness (< Inm), thickness controllable with nm accuracy by the number of dipping cycles and ionic conditions. Functional molecules can be integrated into the films with a position along the surface normal, controlled with nm precision. Depending essentially on electrostatic interactions the technique is applicable to many multiply charged systems: synthetic or natural polymers, proteins, colloidal particles, and dyes. It also does not require planar and flat surfaces. Instead the surface can be rough, porous or strongly curved. Consequently we have developed various protocols to coat colloidal particles by this technique /2/ (Fig. 1). These protocols either exist in incubating the colloidal particles in a

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solution containing more polyelectrolyte than : ^ 1 '^ needed for adsorption and then removing ® "^*J \ ^ ^ excess polyelectrolyte by centrifugation or filtering before adding polyelectrolyte with the pig. 1 Scheme of the layer-by-layer opposite charge, or by adding just sufficient adsorption of polyelectrolytes on colloidal polyelectrolyte as needed for saturation coating, particles. The excess polyelectrolyte in the The conjecture that each adsorption step leads supernatant has to be removed prior to to reversal of the surface charge is verified by adsorption of the next polyion species measurements of the electrophoretic mobility. The coating can be followed quantitatively by single particle light scattering. Fig. 2 shows that the distribution of the scattering intensity per particle shifts to higher values depending on the number of coating processes. This shift can be quantified applying Rayleigh-Debye- 2000 ^ Gans or Mie theory knowing the refractive index of the polymer /3/. One thus derives 15001thickness increases of about 1 nm per step which is close to the value determined by X-ray 10001reflectivity for planar surfaces. One also realizes that there is little broadening of the distribution 500 \ with coating proving that the deposit thickness is the same for different particles. This does not ^, ^ ^, .• • -r TT T 200 300 400 500 600 700 prove that the coating is umform. However, if .,. ^ ^, ij t Scattering Intensity (arb. units) this were not the case one would observe particle aggregation, because there would be 7 Q- i n' 1 1' ht sc tterine Coulomb attraction between oppositely charged . *^* . .^^^f ^ rnccmAo *3 j-^* 11 J -ru- • / u J intensity distnbutions of PSS/PAH coated areas on different colloids. This is not observed , , ^ ir . x 1 * ^'^ r ^Ar\ uru* ^ ' A Auu * polyfstyrene sulfate) latex particles of 640 by light scattenng. A dimer or higher aggregate }• . would appear at higher intensities, in contrast to '^"^ ^^^^ ^^ our findings. Because the basic force for layer build up is electrostatic attraction the wall material can exist of many different, but multiply charged entities. We have demonstrated this versatility using synthetic and natural charged polymers, proteins, inorganic colloids, DNA, charged dyes and trivalent metal ions /4/. Also the colloidal core to be coated can be of many different nature, and this advantage will be apparent below. We have coated successfully latices, biological cells, inorganic particles, precipitates of enzyme, DNA or dyes, and even hydrophobic particles and oils could be coated after rendering their surface charged via adding low or high molecular weight amphiphiles /5/. These cores have become very important since they define conditions under which they can be removed. This process then yields hollow capsules and is possible since generally the polyelectrolyte films are permeable to small molecules but impermeable for macromolecules with molecular weight of some thousands. In the case of weakly cross-linked melamine formaldehyde the core could be removed by going to pH 1 /6/, biological templates were removed via deproteinizer solution, inorganic particles could be removed by milder pH changes, and organic cores were dissolved adding proper solvent /5/. Altogether these different procedures lead to hollow capsules with the following main features - Sizes and size distribution, depending on the template,,, between 70 nm and 10 jim

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Wall thickness tunable in the nm range Wall composition tunable along the surface normal Inner and outer surface variable Variable wall material.

This unique variability should lead to a wide tunability of properties and examples of this will be given in the next section. III. Properties of Hollow Capsules III. 1 Encapsulation and Release Fig. 3 shows a confocal fluorescence micrograph of a hollow capsule after adding a fluorescently labe^._ :,, led polyelectrolyte to the outside aqueous medium /7/. The left image was taken at a pH close to that during Apsjilatid preparation. The daric interior demonstrates that the wall is impermeable for the polyelectrolyte, and this holds over times of at least Fig. 3: Top: Scheme of pH reversible opening and closing of ^ However, polyelectrolyte capsules: Bottom: Confocal fluorescence micrograph j-g^jucing the pH to obtained with fluorescently labeled dextran ^ (middle) the wall becomes permeable as evidenced by the fluorescence fi-om the interior. Increasing the pH again to 8 and removing the outside polyelectrolyte one observes that the polyelectrolyte could be entrapped, i. e. the wall has become impermeable again. This intriguing finding was encountered also for proteins and labeled dextrans with molecular weights fi"om 70 000 to 2.000 000 and can be explained as follows /If: The multilayer is composed of a strong polyelectrolyte, PSS i. e. all dissociable groups are charged, and a weak polyelectrolyte, PAH, where depending on the pH only part of the side groups are charged. At the pH of preparation the negatively and the positively charged groups compensate and the fihn interior is nearly neutral. This is the case for preparation at a pH between 7 and 8. Now reducing the pH more amine groups of PAH become charged and the interior of the fihn is charged up. The intemal Coulombic repulsion will be partly compensated by the counter ions fi-om solution. This yields an intemal osmotic pressure which overall gives a force destabilizing the fihn. This destabilizafion may resuh in disrupture of the fihn or in pore formation which is obviously the case here. The finding of a reversible pore formation is accidental and we would expect that this reversibility cannot be repeated too many times. This is, however, not needed for many practical applications.

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The above arguments indicate that this release threshold can be varied via preparation parameters and type of polyelectrolyte as well as that ionic strength yields another control parameter. This has indeed been found. The above experiment yields parameters for controlled enc^qpsulation and release of macromolecules including proteins. For small molecules (Mw <10^), however, films prepared up to now were largely permeable as measured by confocal microscopy with dye probes in similar experiments as in Fig. 3. Then one may encapsulate by controlled precipitation in an experiment as described with Fig. 4 /8/. In this case the negatively charged dye carboxyfluorescein was used as model drug. The capsule was prepared with the inner surface positively charged, the outer one negatively. The dye in solution is distributed nearly homogeneous inside and outside the capsule but with some enrichment near the inner surface because of Colombic Fig. 4: Electron micrograph of carboxyfluorescein forces. Lowering the pH causes dye precipitates in templated erythrocytes precipitation and this occiu^ predominantly near this inner surface. From there crystal growth proceeds towards the center, more dye is sucked into the inside until the capsule is filled with precipitate. The image in Fig. 4 shows that crystallization occurs exclusively in the inside for weak supersaturation and if the outside is positively charged. In this case even more complicated shapes like the discoidic erythrocytes can be templated (Fig. 4 right). III.2 Mechanical Properties and Stability Fig. 5 shows a sequence of confocal micrographs that enable measurement of the elastic modulus \i. The wall was stained by a fluorescent dye, the polyelectrolyte PSS was added to

Fig. 5 Fluorescence micrograph of hollow shells increasing the concentration of PSS outside fi-om left to right the outside and the sequence corresponds to increasing PSS concentration /9/. Since PSS does not penetrate the capsule it creates an osmotic pressure fi-om outside and this causes deformation. Coimting thefi-actionof deformed capsules one can define a critical pressure Pc where the instability sets in. In a simple model assuming a hollow sphere with radius R

489 and homogeneous wall thickness d one expects a relation P^

•-=-(!)"

(1).

The square dependence on R and 5 could be verified and one thus obtains \i = 500 MPa. This value is somewhat less than that for a glassy polymer like PMMA and we thus may consider the wall like a glassy polymer. Although the above experiment is elegant and meaningful one should not consider \i as typical for the shell material. We have mentioned above that the shell could be composed of many different materials including inorganic particles, and thus \i may vary drastically. However, even for the same material \i may vary, as expected from the above pH variation but also as a function of temperature as revealed from Fig. 6 /lO/. In this case one observes a

Fig. 6: CLSM images (a), (b), and SFM (Contact Mode) topview images (c), (d) of 10-layer (PSS/PAH)5 polyelectrolyte capsules prepared on melamine formaldehyde resin latex solution, (a), (c) before and (b), (d) after annealing at 70°C for 2 h capsule shrinking on increasing the temperature to 70 °C. Detailed analysis of the height profiles from the AFM measurements reveals that this shrinkage is accompanied by a wall thickness increase. Hence the individual layers, initially rather stratified, would like to coil for entropic reasons. A thickness increase at constant density then has to cause a surface area decrease and thus lateral shrinking. The remaining question now is. How is it possible, in view of the many electrostatic bonds in the film, to have a molecular reorientation? Indeed if one assumes that reorientation requires simultaneous breaking of many bonds (say 15), and each bond is screened partly by water (E « 4 0 ) one may estimate with Eyring's theory reorientation times between hours and months and a strong temperature dependence /lO/. On the other hand these estimates show that varying molecular parameters like charge-charge distance or water content in the film one may obtain stability over years or instantaneous instabilities.

490 Another aspect of stability, the so-called colloidal one, that against precipitation can trivially be tuned. The preparation process yields charge stabilized colloids and these are stable in solution at least over months. On the other hand reducing the surface charge, e. g. by adsorbing oppositely charged polyelectrol)^es without reversing the charge eventually causes flocculation, as known in many applications of polyelectrolytes as flocculants. Acknowledgement: We acknowledge the skillful assistance of H. Zastrow and I. Bartsch. The work was supported by the Bundesministerium fiir Forschung imd Technologic, the Senate of Berlin, BMBF grant 03C0293A1 REFERENCES 1. G. Decher, Science, 277 (1997) 1232 2. G. B. Sukhorukov, E. Donath, H. Lichtenfeld, E. Knippel, M. Knippel, H. M6hw3ild,ColLSurf. A, 137(1998)253 F. Caruso, E. Donath, H. Mohwald, J. Phys. Chem. 102 (1998) 2011 3. H. Lichtenfeld, L. Knapschinsky, C. Diirr, H. Zastrow, Progr. Coll. Polym. Sci, 104 (1997) 148 4. G. B. Sukhorukov, E. Donath, S. A. Davis, H. Lichtenfeld, F. Caruso, V. L. Popov, H. Mohwald, Polym. Advan.. Technol 9 (1998) 759 L L. Radtchenko, G. B. Suhorukov, S. Leporatti, G. B. Khomutov, E. Donath, H. Mohwald, J. Col & Int. Sci. 230 (2000), 272-280 A. Rogach, A. Susha, F. Caruso, G. B. Sukhorukov, A. Komowski, S. Kershaw, H. Mohwald, A. Eychmuller, H. Weller, Adv. Mat., 12 (2000) 333 F. Caruso, H. Mohwald, Langmuir, 15 (1999) 8276-8281 F. Caruso, R. A. Caruso, H. Mohwald, Science 282 (1998) 1111-1114 S. Moya, E. Donath, G. B. Sukhorukov, M. Auch, H. Baumler, H. Mohwald, Macromolecules, 33 (20000) 4538-4544 5. G. B. Sukhorukov, N. A. Moroz, N. L Larionova, E. Donath, H. Mohwald, Appl. Biochem. Biotech., (2000),: submitted F. Caruso, D. Trau, H. Mohwald, R. Renneberg, Langmuir, 16 (2000) 1485-1488 F. Caruso, W. Yang, D. Trau, R. Renneberg, Langmuir 2000, in press E. Donath, G. B. Sukhorukov, H. Mohwald, Nach. Chem. Tech. Lab., 47 (1999) 400 A. A. Antipov, G. B. Sukhorukov, S. Leporatti, I. L. Radtchenko, E. Donath, H. Mohwald, Coll. Surf. A. 2000, submitted 6. E. Donath, G. B. Sukhorukov, F. Caruso, S. Davis, H. Mohwald, Angew. Chem. 1998, 2323, Angew. Chemie, Inter. Ed. Eng, 37 (1998) 2201 7. G. B. Sukhorukov, A. A. Antipov, A. Voigt, E. Donath, H. Mohwald, Macromol. Rap. Comm., 2000, in press 8. G. B. Sukhorukov, L. Dahne, J. Hartmann, E. Donath, H. Mohwald, Adv. Mat. 12 (2000) 112-115 9. C. Y. Gao, E. Donath, S. Moya, V. Dudnik, H. Mohwald, Eur. Phys. J. E, 2000, in press. 10. S. Leporatti, C. Y. Gao, A. Voigt, E. Donath, H. Mohwald, submitted to Eur. Phys. J. E., 2000