Layer-by-Layer Assembled Microgel Films with High Loading Capacity

Multilayer films containing microgels of chemically cross-linked poly(allylamine hydrochloride) (PAH) and dextran (named PAH-D) were fabricated by ...
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Langmuir 2008, 24, 1902-1909

Layer-by-Layer Assembled Microgel Films with High Loading Capacity: Reversible Loading and Release of Dyes and Nanoparticles Lin Wang, Xu Wang, Mingfei Xu, Dongdong Chen, and Junqi Sun* State Key Lab of Supramolecular Structure and Materials, College of Chemistry, Jilin UniVersity, Changchun, P. R. China 130012 ReceiVed October 7, 2007. In Final Form: NoVember 18, 2007 Multilayer films containing microgels of chemically cross-linked poly(allylamine hydrochloride) (PAH) and dextran (named PAH-D) were fabricated by layer-by-layer deposition of PAH-D and poly(styrene sulfonate) (PSS). The successful fabrication of PAH-D/PSS multilayer films was verified by quartz crystal microbalance measurements and cross-sectional scanning electron microscopy. The as-prepared PAH-D/PSS multilayer films can reversibly load and release negatively charged dyes such as methyl orange (MO) and fluorescein sodium and mercaptoacetic acidstabilized CdTe nanoparticles. The loading capacity of the film for MO can be as large as ∼3.0 µg/cm2 per bilayer, which corresponds to a MO density of 0.75 g/cm3 in the film. The high loading capacity of the PAH-D/PSS films originates from the cross-linked film structure with sufficient binding groups of protonated amine groups, as well as their high swelling capability by solvent. The loaded material can be released slowly when immersing the films in 0.9% normal saline. Meanwhile, the PAH-D/PSS multilayer films could deposit directly on either hydrophilic or hydrophobic substrates such as quartz, polytetrafluoroethylene, polystyrene, poly(ethylene terephthalate), and polypropylene. The microgel films of PAH-D/PSS are expected to be widely useful as matrixes for loading functional guest materials and even for controlled release.

Introduction In the past decade, the layer-by-layer (LbL) assembly technique has emerged as a versatile and convenient method for the construction of layered ultrathin films with precise control of film thickness and composition. Advanced multilayer film materials with components such as synthetic polymers, biomacromolecules, particles, dentritic molecules, and dyes have been successfully fabricated.1-6 These kinds of layered multilayer films have multiple applications in areas such as antireflection coatings,7 biosensors,8 nonlinear optics,9 solid-state ion-conducting materials,10 solar-energy conversion,11 and permselective * To whom correspondence should be addressed. Phone: 0086-43185168723. Fax: 0086-431-85193421. E-mail: [email protected]. (1) Decher, G.; Schlenoff, J. B. Multilayer Thin Films-Sequential Assembly of Nanocomposite Materials; Wiely-VCH: Weinheim, Germany 2002. (2) Decher, G. Science 1997, 277, 1232. (3) Bertrand, P.; Jonas, A.; Laschewsky, A.; Legras, R. Macromol. Rapid Commun. 2000, 21, 319. (4) Hammond, P. T. AdV. Mater. 2004, 16, 1271. (5) Tang, Z. Y.; Wang, Y.; Podsiadlo, P.; Kotov, N. A. AdV. Mater. 2006, 18, 3203. (6) Zhang, X.; Chen, H.; Zhang, H. Y. Chem. Commun. 2007, 1395. (7) (a) Hiller, J.; Mendelsohn, J. D.; Rubner, M. F. Nat. Mater. 2002, 1, 59. (b) Wang, T. C.; Cohen, R. E.; Rubner, M. F. AdV. Mater. 2002, 14, 1534. (c) Rouse, J. H.; Ferguson, G. S. J. Am. Chem. Soc. 2003, 125, 15529. (d) Cho, J.; Hong, J.; Char, K.; Caruso, F. J. Am. Chem. Soc. 2006, 128, 9935. (8) (a) Sun, Y. P.; Zhang, X.; Sun, C. Q.; Wang, B.; Shen, J. C. Macromol. Chem. Phys. 1996, 197, 147. (b) Lvov, Y.; Caruso, F. Anal. Chem. 2001, 73, 4212. (c) Wang, Y.; Joshi, P. P.; Hobbs, K. L.; Johnson, M. B.; Schmidtke, D. W. Langmuir 2006, 22, 9776. (d) Calvo, E. J.; Danilowicz, C.; Wolosiuk, A. J. Am. Chem. Soc. 2002, 124, 2452. (9) (a) Lvov, Y.; Yamada, S.; Kunitake, T. Thin Solid Films 1997, 300, 107. (b) Kang, E. H.; Jin, P. C.; Yang, Y. Q.; Sun, J. Q.; Shen, J. C. Chem. Commun. 2006, 4332. (c) Jiang, L.; Lu, F.; Chang, Q.; Liu, Y.; Liu, H.; Li, Y.; Xu, W.; Cui, G.; Zhuang, J.; Li, X.; Wang, S.; Song, Y.; Zhu, D. Chem. Phys. Chem. 2005, 6, 481. (d) Van Cott, K. E.; Guzy, M.; Neyman, P.; Brands, C.; Heflin, J. R.; Gibson, H. W.; Davis, R. M. Angew. Chem., Int. Ed. 2002, 41, 3236. (e) Balasubramanian, S.; Wang, X. G.; Wang, H. C.; Yang, K.; Kumar, J.; Tripathy, S. K.; Li, L. Chem. Mater. 1998, 10, 1554. (f) Fischer, P.; Koetse, M.; Laschewsky, A.; Wischerhoff, E.; Jullien, L.; Persoons, A.; Verbiest, T. Macromolecules 2000, 33, 9471. (10) Lowman, G. M.; Tokuhisa, H.; Lutkenhaus, J. L.; Hammond, P. T. Langmuir 2004, 20, 9791.

membranes.12 Recently, much attention has been paid to the loading and release of guest materials within LbL assembled multilayer films. Multilayer films capable of reversible loading and release of guest materials have many kinds of applications, especially in the area of controlled drug release technology.13 For instance, such kinds of films deposited on the surface of bandages, implanted stents,14 and artificial organs can deliver drugs and help the concrescence of wounds, preventing restenosis or thrombus, and so forth. There are generally two kinds of methods to incorporate guest materials into LbL assembled multilayer films to realize controlled release. One is direct alternative deposition of the guest material with an oppositely charged partner species to construct degradable multilayer films or multilayer films capable of releasing guest materials under changed environment conditions.15 The other method involves the first construction of the matrix polyelectrolyte multilayer films and then incorporating the guest materials by a post-diffusion step.16 The latter method is especially suitable for those having few charged or binding groups which cannot be alternatively assembled with a partner species to produce multilayer films. Meanwhile, the latter method makes it possible to recycle the matrix films for repeated loading and release of the guest materials. (11) (a) Guldi, D. M.; Zilbermann, I.; Anderson, G.; Kotov, N. A.; Tagmatarchise, N.; Prato, M. J. Mater. Chem. 2005, 15, 114. (b) Guldi, D. M.; Rahman, G. M. A.; Prato, M.; Jux, N.; Qin, S.; Ford, W. Angew. Chem., Int. Ed. 2005, 44, 2015. (12) (a) Leva¨salmi, J.-M.; McCarthy, T. J. Macromolecules 1997, 30, 1752. (b) Krasemann, L.; Tieke, B. J. Membr. Sci. 1998, 150, 23. (c) Bruening, M. L.; Sullivan, D. M. Chem. Eur. J. 2002, 8, 3833. (d) Park, M.-K.; Deng, S.; Advincula, R. C. J. Am. Chem. Soc. 2004, 126, 13723. (e) Ball, V.; Voegel, J.-C.; Schaaf, P. Langmuir 2005, 21, 4129. (f) Kang, E. H.; Liu, X. K.; Sun, J. Q.; Shen, J. C. Langmuir 2006, 22, 7894. (13) Lynn, D. M. Soft Matter 2006, 2, 269. (14) Jewell, C. M.; Zhang, J.; Fredin, N. J.; Wolff, M. R.; Hacker, T. A.; Lynn, D. M. Biomacromolecules 2006, 7, 2483. (15) (a) Wood, K. C.; Boedicker, J. Q.; Lynn, D. M.; Hammond, P. T. Langmuir 2005, 21, 1603. (b) Zelikin, A. N.; Li, Q.; Caruso, F. Angew. Chem., Int. Ed. 2006, 45, 7743. (c) Ren, K. F.; Ji, J.; Shen, J. C. Bioconjugate Chem. 2006, 17, 77. (d) Recksiedler, C. L.; Deore, B. A.; Freund, M. S. Langmuir 2006, 22, 2811. (e) Thierry, B.; Kujawa, P.; Tkaczyk, C.; Winnik, F. M.; Bilodeau, L.; Tabrizian, M. J. Am. Chem. Soc. 2005, 127, 1626. (f) Niu, J.; Shi, F.; Liu, Z.; Wang, Z. Q.; Zhang, X. Langmuir 2007, 23, 6377.

10.1021/la7031048 CCC: $40.75 © 2008 American Chemical Society Published on Web 01/19/2008

LBL Assembled Microgel Films

Although many types of LbL assembled multilayer films capable of loading guest materials and releasing them in a controlled way were fabricated, several issues concerned with the LbL assembled multilayer films for loading and release of guest materials need to be further addressed. One of the most important issues is how to increase the loading capacity of the matrix films. The thin film nature and the highly ionically cross-linked film structure are usually unfavorable for high loading of guest materials in LbL assembled multilayer films. The low loading capacity of LbL assembled multilayer films will heavily retard the application of LbL assembled films in controlled release technology. With an increase in the number of film deposition cycles, thick films are generally fabricated which can in turn increase the amount of loaded guest materials. But in practice, the diffusion of the guest materials into layered films will become difficult with the increase of the film thickness. Other issues include, for instance, the reversible loading and release of guest materials, the release of the loaded materials under physiological conditions,15a the capability to deposit the matrix films directly on various kinds of substrates without any modification of the substrates, and so forth. Recently, LbL assembled hydrogel films or films containing microgel components have received particular attention because of the stimulus-responsive release behavior of these films. For instances, Sukhishvili and co-workers described the fabrication of surface hydrogel film derived from hydrogen-bonded poly(N-vinylpyrrolidone) (PVPON)/poly(methacrylic acid) (PMAA) multilayers by selective chemical cross-linking of the PMAA units and subsequent removal of PVPON units.17 Akashi and co-workers fabricated ultrathin hydrogel films by utilizing the amide formation reaction during the LbL deposition of poly(acrylic acid-co-N-isopropylacrylamide) and poly(vinylamine hydrochloride).18 Lyon and co-workers describe the preparation of microgel thin films by LbL deposition of poly(N-isopropylacrylamide-co-acrylic acid) microgels with poly(allylamine hydrochloride).19 Responsive hydrogel thin films or films containing microgels can be swollen by solvent in response to various external stimuli, such as temperature, irradiation, pH, and ionic strength of solution. We believe that the cross-linked film structure with sufficient binding groups, as well as their capability of swelling by solvent, can facilitate the incorporation of the guest materials and will guarantee an increased amount of guest materials loaded within the microgel films. In this paper, a new type of microgels of poly(allylamine hydrochloride) (PAH) and dextran (named PAH-D) were synthesized by cross-linking PAH and dextran. PAH-D microgel contains amine groups and can be alternatively deposited with polyanion poly(styrene sulfonate) (PSS) to produce multilayer films of PAH-D/PSS based on electrostatic interaction as the driving force. The as-prepared PAH-D/PSS multilayer films can reversibly load and release negatively charged dyes such as methyl orange (MO) and fluorescein sodium and mercaptoacetic acid(16) (a) Chung, A. J.; Rubner, M. F. Langmuir 2002, 18, 1176. (b) Sato, K.; Suzuki, I.; Anzai, J. Langmuir 2003, 19, 7406. (c) Quinn, J. F.; Caruso, F. Langmuir 2004, 20, 20. (d) Burke, S. E.; Barrett, C. J. Macromolecules 2004, 37, 5375. (e) Berg, M. C.; Zhai, L.; Cohen, R. E.; Rubner, M. F. Biomacromolecules 2006, 7, 357. (f) Guyomard, A.; Nysten, B.; Muller, G.; Glinel, K. Langmuir 2006, 22, 2281. (g) Jiang, S. G.; Chen, X. D.; Liu, M. H. J. Colloid Interface Sci. 2004, 277, 396. (17) Kharlampieva, E.; Erel-Unal, I.; Sukhishvili, S. A. Langmuir 2007, 23, 175. (18) (a) Serizawa, T.; Matsukuma, D.; Nanameki, K.; Uemura, M.; Kurusu, F.; Akashi, M. Macromolecules 2004, 37, 6531. (b) Serizawa, T.; Matsukuma, D.; Akashi, M. Langmuir 2005, 21, 7739. (19) (a) Nolan, C. M.; Serp, M. J.; Lyon, L. A. Biomacromolecules 2004, 5, 1940. (b) Serpe, M. J.; Yarmey, K. A.; Nolan, C. M.; Lyon, L. A. Biomacromolecules 2005, 6, 408. (c) Nolan, C. M.; Serpe, M. J.; Lyon, L. A. Macromol. Symp. 2005, 227, 285.

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stabilized CdTe nanoparticles. The loaded material can be released slowly when immersing the films in 0.9% normal saline. Most importantly, the loading capacity of the film for MO can be as large as ∼3.0 µg/cm2 per bilayer, which corresponds to a MO density of 0.75 g/cm3 in film. Meanwhile, the PAH-D microgel can deposit directly on hydrophilic and hydrophobic surfaces, which guarantees the deposition of the PAH-D/PSS multilayer films on various kinds of substrates such as quartz, polytetrafluoroethylene, polystyrene, poly(ethylene terephthalate), and polypropylene without any substrate modification. Experimental Section Materials. Poly(diallyldimethylammonium chloride) (PDDA, Mw ca. 100000-200000), poly(allylamine hydrochloride) (PAH, Mw ca. 70000), poly(sodium 4-styrenesulfonate) (PSS, Mw ca. 70000), and NaBH4 were purchased from Sigma-Aldrich. Thioglycolic acid (TGA) was purchased from Alfa. Dextran (Mw ca. 40000) was purchased from Tokyo Chemical Industry Co., Ltd. Methyl orange, Rhodamine B, and fluorescein sodium were purchased from Beijing Chemical Reagents Company. The TGA-stabilized CdTe nanoparticles were synthesized according to a literature procedure and their size is about 3.6 nm as confirmed by transmission electron microscopy (TEM).20 All other chemicals were of analytical reagent grade and used as received. Deionized water was used for all the experiments. Synthesis of Microgels of PAH and Dextran (PAH-D). The detailed synthesis procedure of PAH-D is shown in Scheme 1 and is described as follows.21 Dextran (0.27 g, 1.67 mmol of repeat unit) was dissolved in deionized water (5 mL). The solution was first purged with nitrogen gas and then added with KIO4 (0.0315 g, 0.1370 mmol). The mixture was stirred at room temperature for 12 h under the protection of nitrogen gas. In this way, part of the hydroxyl groups in dextran was oxidized into aldehyde groups. Then an excess amount of BaCl2 (∼0.137 mmol) was added to precipitate IO32anions produced during the oxidation reaction. The precipitation of BaIO3 was filtered out. The Ba2+ ions introduced into the reaction solution were removed by adding a proper amount of Na2SO4 (∼0.2 mmol) into the filtrated solution followed with filtration. The solution with partially oxidized dextran was diluted to 25 mL with water. A solution of PAH (0.2336 g, 2.5 mmol in the means of monomer) in H2O (20 mL) was adjusted with NaOH to a pH of 9.8. The solution of partially oxidized dextran was slowly added under stirring to the above-mentioned PAH solution while the PAH solution was purged with nitrogen gas. After complete addition, the solution was allowed to stir for another 2 h under the protection of nitrogen gas. The amine groups of PAH reacted with aldehyde groups of partially oxidized dextran to produce a cross-linked polymer via the formation of imine (-NdC-) bonds. NaBH4 (0.10 g, 2.6 mmol) was finally added to reduce -NdC- into -N-C- and microgels of PAH and dextran (noted as PAH-D) were obtained. The resulted reaction solution was dialyzed against deionized water to remove inorganic impurities. The PAH-D solution was diluted to 100 mL with deionized water. The above-synthesized PAH-D MGs solution (10 mL) was added into isopropanol (50 mL) and the precipitate was collected by centrifugation and washing with a mixture solvent of isopropanol/ ethanol (v:v ) 5:1) three times. The precipitate was dried in a vacuum oven at a temperature of 40 °C for 24 h. Yellowy powder of PAH-D microgels was finally obtained with a yield of ∼93.6%. Therefore, almost all the PAH and dextran reacted to produce the final PAH-D. The synthesized PAH-D contains PAH and dextran with a monomer molar ratio of 1.5:1. Film Preparation. Quartz and silicon wafers were immersed in piranha solution (1:3 mixture of 30% H2O2 and 98% H2SO4) and heated until no bubbles were released. Caution: Piranha solution reacts violently with organic material and should be handled carefully. Ag-coated quartz crystal microbalance (QCM) resonators (20) Zhang, H.; Zhou, Z.; Yang, B.; Gao, M. Y. J. Phys. Chem. B 2003, 107,8. (21) Ma, S. D.; Chen, J. H. Chin. Phaem. J. 2006, 41, 1005.

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Scheme 1. Schematic Illustration of the Synthesis of Microgels of PAH and Dextran

were sonicated slightly in ethanol and water and were dried by N2 flow. Polytetrafluoroethylene (PTFE), polystyrene (PS), poly(ethylene terephthalate) (PET), and polypropylene (PP) were cleaned by sonication in the mixture solution of ethanol, water, and KOH with a mass ratio of 39:60:1 for 30 min, then rinsed with copious amount of water, and finally dried by N2 flow. These cleaned substrates are suitable for LbL deposition of PAH-D/PSS multilayer films without any substrate modification. The deposition of PAHD/PSS multilayer films initiates with the PAH-D layer because its ability to deposit on substrates of almost any surface wettability. The substrate was first immersed in a PAH-D aqueous solution (1.0 mg/mL) for 20 min to obtain a layer of PAH-D, followed by rinsing with water twice for 1 min each time and drying with N2 flow. The substrate was then transferred to an aqueous PSS solution (1.0 mg/ mL) for 20 min, rinsed with water twice for 1 min each time, and blown dry with N2 flow. By repetition of the above deposition processes in a cyclic fashion, multilayer film of PAH-D/PSS can be fabricated. For film deposition on a QCM resonator, a precursor film of (PDDA/PSS)*3 was deposited to eliminate the surface difference among different resonators. The PDDA/PSS film was prepared by immersing the resonator in aqueous PDDA (1.0 mg/ mL) and PSS (1.0 mg/mL) solutions for 20 min alternatively with intermediate water washing. The pH of the PAH-D and PSS solutions was adjusted with either 1 M HCl or 1 M NaOH. Loading and Release of Dyes and Nanoparticles. Loading of the microgel multilayer film was realized by immersing the film into aqueous solution of MO (1.0 or 15.0 mM) and CdTe nanoparticles (0.5 mg/mL). The film was taken out for a given time, rinsed with an ample amount of water, and dried with N2 flow for UV-vis spectroscopy or QCM measurements. The dye-loaded films deposited on quartz slides were immersed into a beaker containing 3 mL of 0.9% normal saline, which was frequently replaced by a fresh one to ensure constant release conditions. The absorbance of released MO in 0.9% normal saline obeyed Beer’s law. The amount of MO

released from the film was determined using a calibration curve for MO in 0.9% normal saline. Characterization. UV-vis absorption spectra were recorded on a Shimadzu UV-2550 spectrophotometer. Dynamic light scattering (DLS) studies and electrophoretic measurements were carried out on a Malvern Nano-ZS zetasizer at room temperature. The measurements were made at a scattering angle of θ ) 173° at 25 °C using a He-Ne laser with a wavelength of 633 nm. QCM measurements were taken with a KSV QCM-Z500 using quartz resonators with both sides coated with Ag (F0 ) 9 MHz). Scanning electron microscopy (SEM) images were obtained on a JEOL JSM 6700F field emission scanning electron microscope. Atomic force microscopy (AFM) images were taken on a commercial instrument, Veeco Company Nanoscope IV. AFM was operated in the tapping mode by using silicon cantilevers with a force constant of 40 N/m. Fourier transform infrared (FT-IR) spectra were collected on a Bruker IFS 66V instrument.

Results and Discussion Synthesis and Characterization of PAH-D Microgels. Scheme 1 depicts the processes for the synthesis of PAH-D microgels. First, part of the hydroxyl groups on dextran was oxidized into aldehyde groups by KIO4. Then the aldehyde groups on dextran react with amine groups of PAH to cross-link dextran and PAH together via the imine formation. The basic reaction solution deprotonates amine groups of PAH and facilitated the reaction. Reduction by NaBH4 turned the unstable carbonnitrogen double bonds (-NdC-) into relatively stable carbonnitrogen bonds (-N-C-) and finally polycationic microgels of PAH and dextran (noted as PAH-D) were obtained. PAH-D microgles were mixed with KBr and pressed to a pellet for FTIR measurements. The absorptions at 1605 and 769 cm-1 result

LBL Assembled Microgel Films

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Figure 2. Typical QCM frequency decreases for the alternative deposition of PAH-D/PSS multilayer films in water solutions at pH ) 7.4 (a), in 0.1 M NaCl solution at pH ) 7.4 (b), in 0.2 M NaCl solution of pH ) 7.4 (c), in 0.2 M NaCl solution of pH ) 8.5 (d), and in 0.2 M NaCl solution of pH ) 10.0 (e). 9 and 2 represents the frequency decreases upon the deposition of PAH-D and PSS, respectively.

Figure 1. pH-dependent size transition (a) and electrophoretic mobility (b) of PAH-D microgels in water without NaCl addition (9) and water added with 0.2 M NaCl (O). The error bar is for standard deviation (n ) 5).

from the scissoring and rocking bending of -N-H of amine groups, which confirm the presence of PAH component in PAH-D microgels. The absorptions at 1019, 1039, and 1152 cm-1 are assigned to the C-O stretching vibrations in dextran, confirming the presence of dextran in PAH-D microgels.21 The absence of carbonyl (CdO) stretching vibration around 1710 cm-1 indicates that no residual aldehyde groups remained in PAH-D microgels.21 The absence of stretching vibration absorption of a carbonnitrogen double bond (-NdC-) peaking around 1615 cm-1 confirms that all carbon-nitrogen double bonds produced in the imine formation reaction were reduced completely by NaBH4.21 The pH-dependent size transition and electrophoretic mobility of PAH-D microgels in water with and without the addition of 0.2 M NaCl were investigated and shown in Figures 1a and 1b, respectively. PAH-D microgels in water at pH 6.0 without NaCl addition have an average hydrodynamic diameter of 471.8 ( 37.2 nm and electrophoretic mobility of +3.8 µm‚cm/V‚s. The hydrodynamic diameter and electrophoretic mobility of PAH-D microgels in water without NaCl addition decrease with the increase of solution pH. At low pH, amine groups in PAH-D microgels are protonated and induced charge-charge repulsion in the network of PAH-D microgels, resulting in swelled microgels. Meanwhile, the protonated amine groups explain the high positive electrophoretic mobility of the microgels. The ratio of amine groups protonated decreases with the increase of solution pH, and so does the intensity of charge-charge repulsion in the network of PAH-D microgels. Therefore, the average hydrodynamic diameter and electrophoretic mobility of PAH-D microgels decrease with increasing solution pH. At pH of 12, almost all amine groups are in the deprotonated state. Meanwhile, hydroxyl groups of PAH-D microgels are deprotonated partially. Therefore, PAH-D microgel has the smallest hydrodynamic diameter of 100.7 ( 10.6 nm and a slightly negative electrophoretic mobility of -0.3 µm‚cm/V‚s in water with a pH of 12 without NaCl addition. The hydrodynamic diameter and electrophoretic mobility of PAH-D microgels in aqueous solution with 0.2 M NaCl added are smaller than those in water without

NaCl addition when the solution pH is the same. The high concentration of inorganic ions can screen the positive charges of protonated amines in PAH-D microgels and reduce the chargecharge repulsion, which leads to a decrease of hydrodynamic diameter and the absolute value of electrophoretic mobility of PAH-D microgels when compared with those in water without NaCl addition. It should be mentioned that when the pH of the microgel solution exceeds 11, the microgels aggregate easily because of the reduced charge-charge repulsion between them. Preparation of PAH-D/PSS Multilayer Films. The electrophoretic mobility showed that PAH-D microgel is positively charged in aqueous solution. Therefore, PAH-D microgel can be LbL assembled with polyanion PSS based on electrostatic interaction as the driving force to prepare PAH-D/PSS multilayer films. QCM measurements were employed to monitor the deposition process of PAH-D/PSS multilayer films. Figure 2 shows the decreases of frequency as a function of the layer number for PAH-D and PSS at different deposition conditions. The deposition conditions were varied by changing the pH and NaCl concentration of PAH-D and PSS dipping solutions. There were five cases investigated: (a) [NaCl] ) 0 mol/L, pH ) 7.4; (b) [NaCl] ) 0.1 mol/L, pH ) 7.4; (c) [NaCl] ) 0.2 mol/L, pH ) 7.4; (d) [NaCl] ) 0.2 mol/L, pH ) 8.5; (e) [NaCl] ) 0.2 mol/L, pH ) 10.0. The pH and NaCl concentration for PAH-D and PSS solutions are the same. In all cases, the QCM frequency regularly decreases because of the successive deposition of PAH-D/PSS multilayers on the resonators. The frequency decreases for the deposition of one layer of PAH-D and PSS were 19.5 ( 5.4 and 21.4 ( 3.8 Hz, respectively, for case (a). With the increase of pH and concentration of NaCl of the dipping solutions, the amount of PAH-D and PSS deposited per deposition cycles increases, as QCM frequency decreases more rapidly. With a NaCl concentration of 0.2 mol/L and solution pH of 10.0, the frequency decreases for the deposition of one layer of PAH-D and PSS increased to be 308.4 ( 94.6 and 338.0 ( 108.1 Hz, respectively. According to the data of size distribution and electrophoretic mobility shown in Figure 1, PAH-D microgel has a greater extension configuration and higher surface charge density in solution with low pH and no NaCl added. The extension configuration and the strong repulsion among neighboring PAH-D caused by their high surface charge density lead to a loosely adsorbed PAH-D layer on the substrate. With the increase of pH and concentration of NaCl added, PAH-D adopts a more contracted configuration and its surface charge density decreases, which in turn leads to a densely adsorbed PAH-D layer on the substrate. Therefore, the amount of PAH-D deposited per

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Figure 3. UV-vis absorption spectra of (PAH-D/PSS)*10 films. (a) As-prepared (PAH-D/PSS)*10 films. (b) Films in (a) after saturation loading of MO molecules. (c) Films in (b) after release of MO molecules. (d) (PAH/PSS)*10 film after saturation loading of MO molecules. Inset shows the absorbance of MO-loaded PAHD/PSS films at 390 nm as a function of the number of film deposition cycles.

deposition cycle increases with the increase of solution pH and concentration of NaCl added in PAH-D solution. The configuration of strong polyelectrolyte of PSS in aqueous solution is mainly affected by ionic strength but not pH of the solution. The amount of PSS deposited per deposition cycle increases with the increase of NaCl added because of the reduced repulsion among PSS chains and coiled configuration, as already described in the literature.22 To realize maximum loading of dyes and nanoparticles in PAH-D/PSS films, the PAH-D/PSS films were fabricated by using a dipping solution of PAH-D and PSS with the addition of 0.2 mol/L NaCl and at a pH of 10.0. Loading and Release of Methyl Orange. Because of their similar molecular weight and dimensions with daily used drugs and their easy detection by spectroscopic means, organic dyes such as methyl orange (MO), fluorescein sodium, and Rhodamine B are frequently employed as model drugs to investigate the loading and release properties of matrix film materials. For example, by using methylene blue as probe molecules, Rubner and co-worker systematically studied the loading and releasing properties of LbL assembled poly(acrylic acid)/poly(allylamine hydrochloride) films.16a The loading and release process of MO in a (PAH-D/PSS)*10 film was monitored by UV-vis absorption spectroscopy. As shown in Figure 3, the as-prepared (PAH-D/ PSS)*10 film has an absorption peaking at 225 nm, which is attributed to the absorbance of benzene groups in PSS. After immersion of the (PAH-D/PSS)*10 film in aqueous 15 mM MO solution (pH ) 7.0, adjusted with 0.1 M sodium acetate buffer) for 12 min, two new absorptions peaking at 274 and 390 nm appear, indicating the successful loading of MO within the (PAHD/PSS)*10 films. Electrostatic interaction of sulfonate groups of MO and protonated amine groups of PAH-D is the main driving force for the loading of MO within (PAH-D/PSS)*10 films. After immersion of the MO-loaded (PAH-D/PSS)*10 films in 0.9% normal saline for 10 h, the absorbance at 274 and 390 nm decreases dramatically, confirming the release of MO in 0.9% normal saline. The electrostatic interaction between MO and protonated amine groups of PAH-D microgel was broken in solution of high ionic strength. Therefore, gradual release of MO from the PAH-D/PSS film was achieved. The inset in Figure 3 shows the absorbance of MO-loaded PAH-D/PSS films at 390 nm as a function of the number of PAH-D/PSS deposition cycles. In each case, a saturation load of MO in the PAH-D/PSS film was realized. The linear increase of the absorbance at 390 nm with the number of film deposition cycles supports that MO (22) Steitz, R.; Leiner, V.; Siebrecht, R.; v. Klitzing, R. Colloids Surf. A 2000, 163, 63.

Figure 4. Time-dependent loading (a) and release (b) profiles of MO molecules in a (PAH-D/PSS)*10 film.

molecules are loaded homogeneously along the normal direction of the whole PAH-D/PSS films. Figures 4 a and 4b shows the loading and release profiles of MO molecules when a (PAH-D/PSS)*10 film is employed, respectively. As shown in Figure 4a, when a 15 mM aqueous MO solution (pH ) 7.0, adjusted with 0.1 M sodium acetate solution) was used, a saturation load of MO molecules in the (PAH-D/PSS)*10 film was achieved with 9 min immersion. This result shows that the incorporation of MO into the PAH-D/PSS multilayer films proceeds very rapidly. The load of MO is concentration-dependent. When a MO aqueous solution with a concentration of 1.0 mM was used, a saturation load of MO molecules in a (PAH-D/PSS)*10 film was achieved after about 8 h of immersion (data not shown). The same saturation load of MO was achieved when using 15 and 1.0 mM MO aqueous solution. When the MO-loaded (PAH-D/PSS)*10 film was immersed in 0.9% normal saline, MO molecules were gradually released from the film. Figure 4b shows the time-dependent release profile of MO molecules from (PAH-D/PSS)*10 films in 0.9% normal saline. The saline was replaced by a fresh one after each measurement was performed. For the initial 1 h, MO was rapidly released, and then the remaining MO was gradually released. After 8-10 h in 0.9% normal saline, approximately 99% of the MO was released from the film, indicating that sustainable release of MO was realized. The maximum loading amount of MO molecules in PAH-D/PSS films is ∼3.0 µg/cm2/bilayer. The PAHD/PSS multilayer films are robust enough for reversible loading and release of MO molecules. The capability of the PAH-D/PSS films for reversible loading and release of MO molecules was evaluated by monitoring the absorbance of the MO retained in the film at 390 nm. As shown in Figure 5, the absorbance at 390 nm fluctuated regularly with the successive loading and release of MO molecules. This result confirms that no dissolution or peeling off of the PAH-D/PSS films occurred during the successive loading and release process of MO molecules. The robustness of PAH-D/PSS films guarantees the recycling usage of PAH-D/PSS films as a matrix for successive loading and release of functional materials. The high stability of PAH-D/ PSS films after successive loading and release of MO molecules

LBL Assembled Microgel Films

Figure 5. Multiple loading and release behavior of a (PAH-D/ PSS)*10 film for MO as monitored by the absorbance at 390 nm. The solid circle (b) represents the absorbance before loading of MO at 390 nm; the solid square (9) represents the absorbance after loading of MO; the solid triangle (2) represents the absorbance after release of MO in 0.9% normal saline.

can be understood as follows: the high ionic strength of saline can break the electrostatic interaction between MO and protonated amines of PAH-D because each MO has only one sulfonate group binding to PAH-D and the electrostatic interaction between them is weak. For each PSS chain, there are many sulfonate groups which can interact with protonated amines of PAH-D. The multiple interactions between PSS and PAH-D could add up to produce an association that is strong enough to maintain the stability of PAH-D/PSS films in 0.9% normal saline. Besides the loading and release of MO molecules, PAH-D/ PSS films can also load negatively charged fluorescein sodium and release it in 0.9% normal saline. The loading of positively charged Rhodamine B into PAH-D/PSS films is unsuccessful, indicating that electrostatic interaction between protonated amine groups of PAH-D microgel and incorporated molecules is the main driving force for dye loading. Structural Characterization of PAH-D/PSS Films. The thickness of a (PAH-D/PSS)*10 film before and after loading of MO molecules was determined form their corresponding crosssectional SEM images. As shown in Figure 6a, the (PAH-D/ PSS)*10 film before MO loading has a constant thickness of 278.3 ( 53.7 nm, corresponding to a thickness of 27.8 nm for one bilayer of PAH-D/PSS. After saturation loading of MO, its thickness increased to be 398.2 ( 32.1 nm, which is ∼1.43 times thicker than its original thickness (Figure 6b). The (PAH-D/ PSS)*10 film before MO loading has a bumpy surface structure, with its surface root mean roughness (rms) being 43.8 nm (Figure 6c). The surface protuberances, which correspond to the aggregations of PAH-D and PSS when adsorbed from aqueous solution with high ionic strength, have a lateral size of 447.8 ( 53.5 nm. The bumpy structures are still observable for the (PAHD/ PSS)*10 film after saturation loading of MO, with the protuberance size increasing to be 714.3 ( 49.4 nm (Figure 6d). The rms of the film after loading of MO increased to be 61.5 nm. Considering that the thickness of the PAH-D/PSS film after MO loading is 39.8 nm per bilayer, the density of loaded MO in the film is as high as 0.75 g/cm3. The value of 0.75 g/cm3 means a high loading capacity of MO within PAH-D/PSS microgel films because the crystallized MO has a density of 1.0 g/cm3. The large loading capacity of the PAH-D/PSS microgel films can be understood as follows: On the one hand, there are many unpaired amine groups in the PAH-D layers, which provide abundant binding sites for MO molecules; on the other hand, slightly cross-linked PAH-D layers make the multilayer film easily swollen in aqueous solution during the adsorption of MO, which facilitate the penetration of MO molecules into the film and guarantee the availability of unpaired amine groups for

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binding of MO molecules. Additionally, the hydrophobic/ hydrophobic interaction between dextran of PAH-D and azobenzene backbone can also favor the loading of MO molecules in the films. For comparison, (PAH/ PSS)*10 film was prepared in the same conditions as that of (PAH-D/PSS)*10 film by the LbL assembly technique. As shown in Figure 3 (curve d), the amount of MO loaded in (PAH/PSS)*10 was far less than that in (PAH-D/PSS)*10 film, confirming that PAH-D microgl is indispensable for increased loading of MO molecules in LbL assembled thin films. Deposition of PAH-D/PSS Multilayer Films on Various Kinds of Substrates. Multilayer films capable of loading guest materials are potentially useful in wide ranges. These films are usually deposited on various kinds of substrates to realize different functionalities. Here the direct deposition of PAH-D/PSS multilayer films on different kinds of substrates such as quartz, polytetrafluoroethylene (PTFE), polystyrene (PS), poly(ethylene terephthalate) (PET), and polypropylene (PP) was examined. To easily verify the deposition of PAH-D/PSS multilayer films on the above-mentioned substrates, the substrates after 10 cycles of PAH-D/PSS deposition were immersed into aqueous MO solution for 12 min. As shown in Figure 7, all the substrates after the deposition of 10 cycles of PAH-D/PSS film and the subsequent immersion in MO aqueous solution have deep orange color. Control experiments showed that no adsorption of MO molecules on these substrates took place without previously alternating dipping these substrates into aqueous solutions of PAH-D and PSS. This result confirms undoubtedly the successful deposition of PAH-D/PSS films on these substrates. The deposition of PAH-D layer on quartz was achieved mainly based on electrostatic interaction and hydrogen bonding between amine groups of PAH-D microgel and silanol groups on a quartz surface. The deposition of PAH-D layer on a hydrophobic surface of PTFE, PS, PET, and PP is mainly based on hydrophobic/hydrophobic interaction between the substrate surface and hydrophobic backbone of PAH16b and dextran in PAH-D microgel. We must point out that the deposition of PAH-D on the above-mentioned substrates is a complex process involving multiple weak interactions. Besides the interactions mentioned above, other kinds of weak interactions such as van der Waals interactions might also contribute to the deposition of PAH-D on various substrates. In some cases, the step for substrate modification is very tedious, especially for hydrophobic and plastic substrates. The capability of direct deposition of PAH-D on various kinds of substrates makes the step for substrate modification simplified and, therefore, will certainly facilitate the application of PAHD/PSS multilayer films. Loading and Release of CdTe Nanoparticles. CdTe nanoparticles with a size of ∼3.6 nm stabilized with thioglycolic acid were employed to mimic the loading and release of drugs with much larger dimensions than MO and fluorescein sodium. QCM measurements show that the value of frequency decrease caused by the loaded CdTe nanoparticles increases linearly with the number of PAH-D/PSS deposition cycles. The average frequency decrease caused by the loaded CdTe nanoparticles within one deposition cycle of PAH-D/PSS is ∼474.1 Hz. This result confirmed that CdTe nanoparticles could penetratee the inner layers of PAH-D/PSS multilayer films, and CdTe nanoparticles were loaded homogeneously along the film normal direction of the whole PAH-D/PSS films. The homogeneous loading of the CdTe nanoparticles in PAH-D/PSS multilayer films was further confirmed by UV-vis spectra of different bilayers of PAH-D/ PSS films after saturation loading of CdTe nanoparticles. The linear increase of the absorbance at 585 nm, which is the typical

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Figure 6. Cross-sectional SEM images of a (PAH-D/PSS)*10 film before (a) and after (b) saturation loading of MO molecules. AFM image (10 × 10 µm) of the same film before (c) and after (d) saturation loading of MO molecules. The scale bar in SEM images corresponds to 1 µm.

Figure 7. Photographs of a (PAH-D/PSS)*10 film deposited on different kinds of substrate after loading of MO molecules: (a) quartz, (b) polytetrafluoroethylene (PTFE), (c) poly(ethylene terephthalate) (PET), (d) polystyrene (PS), and (e) polypropylene (PP).

absorbance of CdTe nanoparticles, confirms that the amount of CdTe nanoparticles loaded in each bilayer is almost equal and supports the QCM result. Photoluminescent spectra of PAHD/PSS multilayer films loaded with CdTe nanoparticles show typical strong emission of CdTe nanoparticles peaking at 636 nm, confirming that chemically intact CdTe nanoparticles were loaded within PAH-D/PSS multilayer films. The loading and release kinetics of CdTe nanoparticles within (PAH-D/PSS)*10 films was monitored by QCM measurements and is shown in Figure 8. The saturation load of CdTe nanoparticles took 6-7 h. QCM measurements showed that the loaded CdTe nanoparticles had a mass ratio of ∼47.5% of the original (PAH-D/PSS)*10 films if the difference of water content in the film before and after CdTe loading is neglected. When (PAH-D/PSS)*10 films loaded with CdTe nanoparticles were immersed in 0.9% normal saline, CdTe nanoparticles were gradually released (Figure 8). After 28 h immersion, about 95% of loaded CdTe nanoparticles were released from the films. The release rate of CdTe

Figure 8. Time-dependent loading (a) and release (b) profiles of CdTe nanoparticles in a (PAH-D/PSS)*10 film.

nanoparticles is slower than that of MO molecules. The slower release rate of CdTe nanoparticles can be explained by the fact that each CdTe nanoparticle contains many carboxylate groups, which produce strong electrostatic/hydrogen bonding interaction with amine groups in PAH-D/PSS films. The successful loading and release of CdTe nanoparticles in PAH-D/PSS multilayer films promise that polymer drugs and functional materials with large sizes can also be incorporated into PAH-D/PSS matrix films for sustainable release.

Conclusions In the present study, we show that microgel films of PAHD/PSS capable of reversible loading and release of negatively charged dyes such as methyl orange (MO) and fluorescein sodium and mercaptoacetic acid-stabilized CdTe nanoparticles can be fabricated by a LbL deposition process. The cross-linked film structure with sufficient binding groups of protonated amine groups, as well as the high swelling capability by solvent, guarantees the high loading capacity of negatively charged guest

LBL Assembled Microgel Films

materials within the microgel films. By breaking the electrostatic interaction between protonated amine groups of PAH-D microgels and the loaded materials, sustainable release of the loaded materials under physiological conditions was realized. LbL assembled microgel films of PAH-D/PSS can be, in principle, deposited on surfaces with complicated morphologies. The high loading capacity, the sustainable release of the loaded materials under physiological conditions, and the capability of depositing the films directly on either hydrophilic or hydrophobic substrates with complicated surface morphology might make the PAH-D/PSS films widely useful as a matrix for loading functional materials and their controlled release.

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Acknowledgment. This work is supported by the Foundation for the Author of National Excellent Doctoral Dissertation of P. R. China (FANEDD Grant No. 200323), National Basic Research Program (2007CB808000), the Program for New Century Excellent Talents in University (NCET), and the Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT Grant No. IRT0422). Supporting Information Available: Calibration curve of methyl orange in 0.9% normal salineand absorbance of the CdTe nanoparticleload (PAH-D/PSS)*n films at 585 nm as a function of the number of film deposition cycles. This material is available free of charge via the Internet at http://pubs.acs.org. LA7031048