Article pubs.acs.org/IECR
Aggregation-Resistant Superparamagnetic Noncovalent Hybrid Multilayer Hollow Microcapsules in High Ionic Strength Media Peng Liu,*,
†
Xiaorui Li,
†
Bin Mu,‡ Pengcheng Du,
†
Xubo Zhao,
†
and Zhuliang Zhong
†
†
State Key Laboratory of Applied Organic Chemistry and Institute of Polymer Science and Engineering, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China ‡ Center of Eco-material and Green Chemistry, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China ABSTRACT: In order to avoid the aggregation and/or fusion of the polyelectrolyte multilayer hollow microcapsules selfassembled via the noncovalent bonds, superparamagnetic polyelectrolyte hybrid hollow microcapsules surface-modified with polyethylene glycol (PEG) brushes were designed and fabricated. After the layer-by-layer (LbL) self-assembly of chitosan (CS) and citric acid-modified magnetic nanoparticles (Fe3O4−CA) as the polycation and the hybrid anion on the polystyrene sulfonate microsphere (PSS) templates, respectively, the aldehyde group terminated polyethylene glycol-4000 (APEG) was grafted onto the surface of the superparamagnetic polyelectrolyte hybrid multilayer coated template microspheres via the nucleophilic addition between the aldehyde groups of APEG and the amino groups of CS. Then, the modified superparamagnetic polyelectrolyte hybrid hollow microcapsules were obtained after the templates were removed by dialysis. It was found that the surface PEGylation could prevent aggregation among the hollow microcapsules in the media with high salt concentration by dynamic light scattering (DLS), besides the increase in biocompatibility. The technique developed is expected to realize the application of the polyelectrolyte multilayer hollow microcapsules in real physiological environments.
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INTRODUCTION Research into polymeric microcapsules with functional performance has already become an important development direction of colloidal particle systems due to their potential applications, especially for the controlled delivery of drug and gene. Various synthetic routes have been developed to prepare polymeric1−3 or hybrid4,5 hollow microcapsules with environmental stimuli-responsive characteristics. The approach, in which the colloidal nanoparticles are introduced into the capsule shells of the multilayer hollow microcapsules by employing electrostatic forces between the nanoparticles and the oppositely charged layer,6,7 is proved to be a promising approach to prepare the hybrid multilayer hollow microcapsules with the special functions. The nanoparticles can be either adsorbed or synthesized directly at the surface of the multilayer coated templates and their distribution can be controlled.8 Aimed at the application of the delivery of drug and genes, the incorporation of magnetic nanoparticles could provide magnetic-targeted9 and/or magnetic-sensitive remote controlled releasing characteristics.10 However, the polyelectrolyte hollow microcapsules based on the noncovalent bonds such as electrostatic attraction and hydrogen bonding between alternating polyelectrolyte layers would give rise to disintegration,11 aggregation,12 and fusion13 in the solution with the strong pH media and higher salt concentration. Furthermore, the aggregation is irreversible.14 These shortcomings of the polyelectrolyte hollow microcapsules based on noncovalent bonds (electrostatic attraction and hydrogen bonding) seriously restrict their practical application in the human physiological environments. Usov et al. modified the layer-by-layer assembled polyelectrolyte microcapsules with dextran and dextran polyaldehyde to © 2012 American Chemical Society
provide stability against aggregation in 0.75 M aqueous solutions of the mono- and bivalent ions.15 Our groups also successfully prepared the polymeric hollow microcapsules with pH/ionic strength/temperature multiresponsive shells via the combination of the layer-by-layer assembly techniques and grafting polymerization of N-isopropylacrylamide (NIPAm).16 The introduction of the poly(N-isopropylacrylamide) (PNIPAm) brushes on the polyelectrolyte shells not only achieved the controlled release of drug molecules which could be dually controlled by solution pH and temperature but also prevented the flocculation among the obtained multiresponsive hollow microcapsules in the solution with higher salt concentration. Poly(ethylene glycol) (PEG) is one of the most commonly used hydrophilic polymers possessing highly biocompatibility which can be rapidly and spontaneously cleared from human bodies as an excellent candidate for biomedical materials.17 It was successfully used to stabilize smaller nanoparticles.18 In the present paper, we modified the superparamagnetic polyelectrolyte hybrid hollow microcapsules with the aldehyde group terminated PEG (APEG) to prevent their aggregation and fusion in the higher salt concentration media (Scheme 1). The results indicated that the surface PEGylation could effectively prevent the agglomeration of the polyelectrolyte hybrid hollow microcapsules in aqueous medium with high ionic strength. Received: Revised: Accepted: Published: 13875
April 13, 2012 October 10, 2012 October 11, 2012 October 11, 2012 dx.doi.org/10.1021/ie301926m | Ind. Eng. Chem. Res. 2012, 51, 13875−13881
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Scheme 1. Preparation of the Aggregation-Resistant Superparamagnetic Polysaccharide Hybrid Hollow Microcapsules ((CS/ Fe3O4−CA)3−CS−g-PEG) in High Ionic Strength Media
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precipitated with excess ether and filtered to obtain the white precipitate. After the white precipitate was dissolved in the dichloromethane and reprecipitated with excess ether once again, the final product, single aldehyde group terminated polyethylene glycol-4000 (APEG), was filtered and dried at 35 °C in vacuum. Polystyrene Sulfonate Microspheres (PSS). The soapfree emulsion polymerization technique was used to prepare the uniform polystyrene microspheres (PS).21 Typically, 5.0 mL ammonium persulfate (APS, 0.054 g) aqueous solution was added dropwise slowly to the mixture containing 10.0 mL styrene, 2.0 mL methacrylic acid, and 95 mL deionized water in N2 atmosphere. The reaction was conducted at 72 °C for 24 h under mechanical stirring. The obtained polymer was centrifuged at 10 000 rpm, and then, the PS microspheres were washed with water four times and finally dried at 50 °C in vacuum to get the white powder. A 2.0 g portion of PS microspheres were ultrasonically dispersed in 60 mL sulfuric acid (98%) and stirred magnetically at 45 °C for 8 h. The reacting solution was diluted with a large number of water after being cooled to room temperature. Next, a sodium carbonate aqueous solution (25 wt %) was added to the reacting mixture until the pH value of the solution reached natural. Then, the final product, the polystyrene sulfonate microspheres (PSS), was centrifuged at 10 000 rpm and washed with water four times and finally dispersed in water for the following experiment. Self-assembling Procedure. The magnetic polyelectrolyte hybrid multilayer-coated polystyrene sulfonate microspheres (PSS@(CS/Fe3O4−CA)3) were prepared via layer-by-layer self-assembly with natural CS with the citric acid modified magnetic nanoparticles (Fe3O4−CA) as polycation and hybrid anion, respectively (Scheme 1): First, the self-assembly of CS on the surface of the PSS templates was completed via the electrostatic interactions of the carboxylic groups and sulfonic acid groups on the surface of PSS and the amino groups of CS.
EXPERIMENTAL SECTION Materials. Chitosan (CS, viscosity-average molecular weight: 6.0 × 105, degree of deacetylation: 90%) was purchased from the Zhengjiang Yuhuan Marine Biotechnology Company. Polyethylene glycol 4000 (PEG 4000) was analytical purity grade, purchased from the Shanghai Wulian Chemical Factory. Styrene (St), methacrylic acid (MAA), N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), acetic anhydride, ether, trichloromethane (CHCl3), dichloromethane (CH2Cl2), ferric chloride hexahydrate (FeCl3·6H2O), ferrous chloride tetrahydrate (FeCl2·4H2O), sodium citrate (CA), ammonia− water (NH3·H2O, 28 wt %), ammonium persulfate (APS), sulfuric acid (H2SO4, 98%), and sodium carbonate (Na2CO3) were analytical reagent grade purchased from Tianjin Chemical Company in China. Deionized water was used throughout. Citrate Acid Modified Magnetic Nanoparticles (Fe3O4−CA). The citrate acid modified Fe3O4 nanoparticles (Fe3O4−CA) were prepared with a modified method based on the work reported previously.19 Briefly, FeCl3·6H2O (26.0 g) and FeCl2·4H2O (9.56 g) with a molar ratio of 2:1 were dissolved into 400 mL deionized water with agitation under N2 protection in a three-necked flask. A mixture of 50 mL NH3·H2O and 50 mL deionized water was added dropwise slowly to the flask after the mixture was heated to 70 °C. After 48 mL, 2 mol/L sodium citrate solution was quickly added, and the reaction was conducted at 70 °C for 5 h. The mixture was heated to 85 °C to remove the remaining ammonia. Finally the Fe3O4−CA nanoparticles were washed until neutral and dispersed in water. Single Aldehyde Group Terminated Polyethylene Glycol-4000 (APEG).20 A 10 g portion of PEG4000 was dissolved in the mixture containing 25 mL DMSO and 10 mL trichloromethane in a flask, then 3.5 mL acetic anhydride was added dropwise slowly to the flask and the solution was magnetically stirred at 35 °C for 10 h. The solution was 13876
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Figure 1. TEM images of (a) PSS@(CS/Fe3O4−CA)1, (b) PSS@(CS/Fe3O4−CA)2, (c) PSS@(CS/Fe3O4−CA)3, (d) (CS/Fe3O4−CA)3, and (e) (CS/Fe3O4−CA)3−CS−g-PEG.
(PSS@(CS/Fe3O4−CA)3−CS) to introduce plentiful surface amino groups for the following graft of APEG. After the PSS@(CS/Fe3O4−CA)3−CS were dispersed in 400 mL deionized water, the excess of APEG were added to the dispersion after the pH of solution was adjusted to 5.0. The reaction was carried out at 30 °C for 24 h under stirring, and then, the microspheres were washed with water several times to remove the free APEG by using the magnetic separation. The product was dried at 50 °C in vacuum for 24 h to get the PEG modified magnetic polyelectrolyte hybrid multilayer encapsulated PSS microspheres (PSS@(CS/Fe3O4−CA)3−CS−gPEG). To obtain the multifunctional superparamagnetic polyelectrolyte hybrid hollow microcapsules, the sacrificial templates (PSS) were removed by dialysis: the PSS@(CS/Fe3O4−CA)3− CS−g-PEG aqueous dispersion was dialyzed against DMF and deionized water using a dialysis membrane (MWCO = 14 000) for 3 days with several changes of DMF and deionized water, respectively. The absence of the templates was confirmed by mixing the final dialysate with three times volume of water ensuring the absence of any precipitate. The final products, the
A pH 5.0 acetic acid solution (100 mL) containing 0.25 g CS was added to 400 mL aqueous dispersion containing 0.5 g PSS, and the mixture was stirred for 6 h to finish the adsorption of CS. Then, the core/shell microspheres were centrifuged at 10 000 rpm and washed with water four times to remove the dissociated polyelectrolyte to obtain the PSS templates coated with chitosan (PSS@CS). Next, the PSS@CS was dispersed into 400 mL deionized water. The citric acid modified magnetic nanoparticles (Fe3O4−CA) were then added under stirring for 6 h. The core/shell microspheres were centrifuged at 10 000 rpm and washed with water four times to obtain the magnetic polyelectrolyte hybrid coated polystyrene sulfonate microspheres (PSS@(CS/Fe3O4−CA)1). Then, chitosan and Fe3O4−CA were alternately deposited two more times onto the core/shell above-mentioned microspheres to obtain the CS/Fe3O4−CA trilayer encapsulated PSS microspheres (PSS@(CS/Fe3O4−CA)3). At last, CS was adsorbed on the surface of the PSS@(CS/Fe3O4−CA)3 again to produce the magnetic polyelectrolyte hybrid trilayer encapsulated PSS microspheres coated with chitosan 13877
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The FTIR spectrum of the PSS@(CS/Fe3O4−CA)3, as shown in Figure 2, revealed that the well-defined characteristic
PEG modified superparamagnetic polyelectrolyte hybrid hollow microcapsules ((CS/Fe3O4−CA)3−CS−g-PEG), were centrifuged, washed with ethanol, and dried under vacuum at 40 °C for 24 h. For comparison, the magnetic polyelectrolyte hybrid hollow microcapsules without PEGylation ((CS/Fe3O4−CA)3) were also prepared from the PSS@(CS/Fe3O4−CA)3 microspheres by the similar process. Analysis and Characterizations. A Bruker IFS 66 v/s infrared spectrometer was used for the Fourier transform infrared (FTIR) spectroscopy analysis in the range of 400− 4000 cm−1 with a resolution of 4 cm−1. The KBr pellet technique was adopted to prepare the sample for recording the IR spectra. The UV−vis spectra of the hollow microcapsules were recoreded by a Perkin-Elmer Lambda 35 UV/vis Spectrometer (Perkin-Elmer Instruments, USA) with aqueous dispersions. The morphologies of the magnetic polyelectrolyte hybrid multilayer encapsulated PSS microspheres (PSS@(CS/Fe3O4− CA)3−CS), magnetic polyelectrolyte hybrid hollow microcapsules (CS/Fe3O4−CA)3, and PEG modified superparamagnetic polyelectrolyte hybrid hollow microcapsules ((CS/ Fe 3 O 4 −CA) 3 −CS−g-PEG) were characterized with a JEM1200 EX/S transmission electron microscope (TEM). The sample were dispersed in water and then deposited on a copper grid covered with a perforated carbon film. The mean particle sizes and size distributions of the hollow microcapsules (CS/Fe3O4−CA)3 and (CS/Fe3O4−CA)3−CS− g-PEG were characterized with by the dynamic light scattering (DLS) on the “Light Scattering System BI-200SM, Brookhaven Instruments” device equipped with the BI-200SM goniometer, the BI-9000AT correlator, temperature controller, and the Coherent INOVA 70C argon ion-laser at 25 °C. DLS measurements are performed using 135 mW intense laser excitation at 514.5 nm and at a detection angle of 90° using the emulsion directly at 25 °C. Magnetic properties of the Fe3O4−CA, PSS@(CS/Fe3O4− CA)3−CS, (CS/Fe3O4−CA)3 and (CS/Fe3O4−CA)3−CS−gPEG samples were detected by vibrating sample magnetometer (Lakeshore 7304). The hysteresis of the magnetization was obtained by changing H between +11 000 and −11 000 Oe at room temperature. The XRD patterns of the Fe3O4−CA, (CS/Fe3O4−CA)3 and (CS/Fe3O4−CA)3−CS−g-PEG samples were recorded in the range of 2θ = 20−70° by step scanning with a Shimadzu XRD6000 X-ray diffractometer using Cu Kα radiation.
Figure 2. FTIR spectra of PSS@(CS/Fe3O4−CA)3, PSS@(CS/ Fe3O4−CA)3−CS−g-PEG, (CS/Fe3O4−CA)3, and (CS/Fe3O4− CA)3−CS−g-PEG.
absorbance bands of polystyrene at 3080, 3060, 3020 (C−H, stretching vibration); 1600, 1490, 1450 (CC, stretching vibration); 700 (out-of-plane blending vibration, δring); and the two characteristic peaks at 1700 and 1080 cm−1 are attributed to the carbonyl stretching of the carboxyl groups of MAA and sulfonic acid groups, respectively. Furthermore, the typical absorbance band of the Fe−O stretching vibration at 580 cm−1 of Fe3O4 (magnetite) can also be found from the IR spectrum of the PSS@(CS/Fe3O4−CA)3.19 This indicated that the magnetic nanoparticles were embodied in the superparamagnetic polysaccharide hybrid hollow microcapsules before and after surface PEGylation. In order to improve the dispersion stability in high ionic strength media of the noncovalent-forced magnetic polyelectrolyte hybrid multilayered hollow microcapsules, the single aldehyde group terminated polyethylene glycol-4000 (APEG) was grafted onto the magnetic polyelectrolyte hybrid shells via the nucleophilic addition between the aldehyde groups of APEG and the amino groups of CS. The absorbance band at 1100 cm−1 of the ethylene ether (C−O−C) structure of PEG appeared in the FTIR spectrum of the products (PSS@(CS/ Fe3O4−CA)3−CS−g-PEG) (Figure 2a).22 This indicated that APEG had been successfully grafted onto the surfaces of the core−shell microspheres. Then, the templates were removed by dialysis with DMF to obtain the multifunctional magnetic polyelectrolyte hybrid multilayered hollow microcapsules ((CS/Fe3O4−CA)3−CS−gPEG). In the TEM images of the core/shell microspheres PSS@(CS/Fe 3 O 4 −CA) 1 , PSS@(CS/Fe 3 O 4 −CA) 2 , and
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RESULTS AND DISCUSSION The magnetic polyelectrolyte hybrid multilayer encapsulated PSS microspheres (PSS@(CS/Fe3O4−CA)n) were prepared via the layer-by-layer self-assembly of the natural CS as the polycation and the citric acid modified magnetic nanoparticles (Fe3O4−CA) as the hybrid anion, respectively. The TEM image of PSS@(CS/Fe3O4−CA)n is shown in Figure 1. It can be found that the diameter of the PSS@(CS/Fe3O4−CA)1 is 180−190 nm, and the diameter of the PSS@(CS/Fe3O4−CA)n increased gradually with the increase in the layer number of Fe3O4−CA and CS. The diameter of the PSS@(CS/Fe3O4− CA)2 and PSS@(CS/Fe3O4−CA)3 is about 200 and 250 nm, respectively. It also inferred that the magnetic hybrid polyelectrolytes were successfully self-assembled on the surface of the PSS templates. 13878
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PSS@(CS/Fe3O4−CA)3, the gray background could be seen. It also could be found that the surface black dots (magnetic nanoparticles) increased with the increasing of the assembling times. After the etching, the gray background disappeared in the images of the (CS/Fe3O4−CA)3 and (e) (CS/Fe3O4− CA)3−CS−g-PEG, which indicated that the PSS templates were removed. Comparing the FTIR spectra of the core/shell microspheres ((PSS@(CS/Fe3O4 −CA) 3 and PSS@(CS/ Fe3O4−CA)3−CS−g-PEG)) with the hollow microcapsules ((CS/Fe3O4−CA)3 and (CS/Fe3O4−CA)3−CS−g-PEG), one can find that the characteristic absorbance bands of polystyrene at 3080, 3060, and 3020 cm−1 disappeared after the etching, while the absorbance bands at 1600, 1490, 1450, and 700 cm−1 partially remained. This might be ascribed to the oligomer of styrene and MAA that adsorbed onto the polyelectrolyte hybrid multilayers.14 The hollow structure of the (CS/Fe3O4−CA)3−CS−g-PEG hollow microcapsules could be observed by TEM (Figure 1). The mean diameter of the (CS/Fe3O4−CA)3−CS−g-PEG hollow microcapsules is about 240 nm. The core/shell PSS@(CS/Fe3O4−CA)3 microspheres were also dialyzed to remove the templates to obtain the magnetic polyelectrolyte hybrid hollow microcapsules without PEGylation ((CS/ Fe3O4−CA)3) for the comparison with the (CS/Fe3O4− CA)3−CS−g-PEG hollow microcapsules, as shown in Figure 1. The diameter of the (CS/Fe3O4−CA)3 hollow microcapsules is around 210 nm. It was smaller than that of the PSS@(CS/ Fe3O4−CA)3 due to the temoval of the templates. The particle size of the (CS/Fe3O4−CA)3−CS−g-PEG hollow microcapsules is bigger than that of the (CS/Fe3O4−CA)3 due to the PEG brushes grafted. In the dried state, the PEG brushes might wriggle into the hybrid shells, so the particle size increased. Furthermore, the absorbance band at 1100 cm−1 of the ethylene ether (C−O−C) structure in the FTIR spectrum of the (CS/Fe3O4−CA)3−CS−g-PEG (Figure 2b) and the two adsorbance peaks at about 250 (π−π*, CN) and 350 nm (nπ, CN) in the UV−vis spectrum (Figure 3) of the final
hybrid multilayered hollow microcapsules ((CS/Fe3O4−CA)3− CS−g-PEG and (CS/Fe3O4−CA)3) are shown in Figure 4. The
Figure 4. Magnetization curves of the Fe3O4−CA, PSS@(CS/Fe3O4− CA)1, PSS@(CS/Fe3O4−CA)2, PSS@(CS/Fe3O4−CA)3, PSS@(CS/ Fe3O4−CA)3−CS−g-PEG, (CS/Fe3O4−CA)3, and (CS/Fe3O4− CA)3−CS−g-PEG.
magnetic remanences of the hollow microcapsules (CS/ Fe3O4−CA)3 and (CS/Fe3O4−CA)3−CS−g-PEG were less than 0.5 emu/g, indicating the near superparamagnetic property.24 The saturation magnetization of the Fe3O4−CA, PSS@(CS/Fe3O4−CA)1, PSS@(CS/Fe3O4−CA)2, PSS@(CS/ Fe3O4−CA)3, PSS@(CS/Fe3O4−CA)3−CS−g-PEG, (CS/ Fe3O4−CA)3, and (CS/Fe3O4−CA)3−CS−g-PEG are 63.32, 10.00, 22.13, 38.26, 35.97, 40.06, and 39.26 eum/g, respectively. Compared with the Fe3O4−CA nanoparticles, the decrease in the saturation magnetization of the (PSS@(CS/ Fe3O4−CA)n and the polyelectrolyte hybrid hollow microcapsules was ascribed to the existence of the PSS, CS, and PEG ingredients. The magnetic contents of the PSS@(CS/Fe3O4−CA)1, PSS@(CS/Fe 3 O 4 −CA) 2 , PSS@ (CS/Fe 3 O 4 −CA) 3 , PSS@(CS/Fe3O4−CA)3−CS−g-PEG, (CS/Fe3O4−CA)3, and (CS/Fe3O4−CA)3−CS−g-PEG are 15.8%, 35.0%, 60.4%, 56.8%, 63.3%, and 62.0%, respectively, calculated from the saturation magnetizations. It suggested that the magnetic saturation intensity increased with the increase in adsorption number of the Fe3O4−CA nanoparticles. It also can be calculated that the content of PEG in the (CS/Fe3O4− CA)3−CS−g-PEG is about 1.3%. The XRD patterns of the Fe3O4−CA, PSS@(CS/Fe3O4− CA)3−CS−g-PEG, and (CS/Fe3O4−CA)3−CS−g-PEG are shown in Figure 5. It can be seen that their patterns are identical, indicating that the structure of the magnetic nanoparticles stays essentially unchanged during the preparation procedure. All the diffraction peaks of the PSS@(CS/ Fe3O4−CA)3−CS−g-PEG and (CS/Fe3O4−CA)3−CS−g-PEG are in good agreement with that of the standard Fe3O4 with diffraction peaks of 220, 311, 400, 422, 511, and 400. It also shows that the magnetic particles are of high crystalline cubic structure.25 In the preparation of the magnetic hybrid polyelectrolyte hybrid hollow microcapsules, we found that they can be fast gathered to one side of the magnet after the application of a localized magnetic field to complete the separation, and it will
Figure 3. UV−vis spectra of the (CS/Fe3O4−CA)3 and (CS/Fe3O4− CA)3−CS−g-PEG.
products indicated that the PEG brushes had been successfully grafted onto the polyelectrolyte hybrid multilayer shells via the Schiff base bonds,23 compared with that of the (CS/Fe3O4− CA)3. The magnetization curves of the Fe3O4−CA nanoparticles, the chitosan/ferroferric oxide magnetic polyelectrolyte hybrid multilayer encapsulated polystyrene sulfonate templates (PSS@(CS/Fe3O4−CA)n) and the magnetic polyelectrolyte 13879
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Table 1. Polydispersity Index (μ2/Γ2) of the Samples polydispersity index (μ2/Γ2) samples PSS PSS@(CS/Fe3O4−CA)1 PSS@(CS/Fe3O4−CA)2 PSS@(CS/Fe3O4−CA)3 PSS@(CS/Fe3O4−CA)3− CS−g-PEG (CS/Fe3O4−CA)3 (CS/Fe3O4−CA)3−CS−gPEG
in 0 mol/L NaCl solution
in 0.20 mol/L NaCl solution
0.005 0.005 0.005 0.005 0.005
0.005 0.184 0.263 0.384 0.005
0.005 0.005
0.441 0.005
Figure 5. XRD patterns of the Fe3O4−CA, PSS@(CS/Fe3O4−CA)3− CS−g-PEG, and (CS/Fe3O4−CA)3−CS−g-PEG.
Figure 6. Ionic strength dependence of the average hydrodynamic diameter (Dh) and polydispersity index (μ2/Γ2) of the (CS/Fe3O4− CA)3−CS−g-PEG (1) and the (CS/Fe3O4−CA)3 (2).
adsorption layers of the hybrid bilayers, while the PSS remained 0.005 due to the nonexistence of polyelectrolyte on their surfaces. However, after grafting PEG brushes on their surfaces, the index of the PSS@(CS/Fe3O4−CA)3−CS−g-PEG also remained constant. The polydispersity index (μ2/Γ2) of the (CS/Fe3O4−CA)3 increased gradually with the increase of the ionic strength from 0.005 to 0.441 (Figure 6), which indicated that the hollow microcapsules aggregated during the process of measurement as reported previously.27 The data were higher than that of the core/shell microspheres PSS@(CS/Fe3O4− CA)3, which might be due to the stabilization of the PSS templates. However, the μ2/Γ2 of the (CS/Fe3O4−CA)3−CS− g-PEG was a constant (0.005) with the increase of the ionic strength in the same range. The small polydispersity index suggested that the size distribution of the modified hollow microcapsules is fairly monomodal.28 The changes of the particle size and the polydispersity index demonstrated that the grafted PEG brushes could effectively prevent aggregation among the obtained superparamagnetic hybrid hollow microcapsules in the media with higher ionic strength. This indicated that the PEG modified superparamagnetic polyelectrolyte hybrid hollow microcapsules ((CS/Fe3O4−CA)3−CS−gPEG) could be applied in real physiological environments. Furthermore, their biocompatibility might be improved via the surface-modification with PEG,29 and the hollow microcapsules ((CS/Fe3O4−CA)3−CS−g-PEG) are completely biodegradable, compared with previous work with PNIPAm.16
has played a great impact on the size of the polyelectrolyte hybrid hollow microcapsules. Along with the increase in the salt concentration from 0 to 0.20 mol/L, the diameter of the (CS/ Fe3O4−CA)3−CS−g-PEG increased from 255 to 329 nm, while that of the (CS/Fe3O4−CA)3 increasd from 201 to 294 nm. The lower particle size change of the (CS/Fe3O4−CA)3−CS− g-PEG must have resulted from the PEG brushes grafted. It is well-known that the ionic strength of the polyelectrolyte solution depends on the concentration of polyelectrolyte and small electrolyte molecules. The small molecule electrolytes could weaken the electrostatic repulsion and the salt bond among the polyelectrolyte multilayered shells of the hollow microcapsules. Therefore, the polyelectrolyte chains stretched and the size of obtained hollow multilayered microcapsules would increase because the small molecule electrolytes usually had a shielding effect on the electrostatic force.26 The polydispersity indexes (μ2/Γ2) of the samples in 0 and 0.20 mol/L NaCl solution were summarized in Table 1. The index increased much higher with the increasing of the
CONCLUSIONS PEG was grafted onto the surface of the superparamagnetic polyelectrolyte hybrid hollow microcapsules fabricated via the noncovalent layer-by-layer self-assembly of chitosan and the citric acid-modified magnetic nanoparticles onto the sacrificial templates. In addition to improving their biocompatibility, the dynamic light scattering analysis indicated that the surface PEG brushes grafted could effectively prevent aggregation and fusion among the superparamagnetic hybrid hollow microcapsules in the high ionic strength media. It is expected the at the biocompatible and biodegradable superparamagnetic polyelectrolyte hybrid hollow microcapsules ((CS/Fe3O4−CA)3−CS− g-PEG) could be applied in the real physiological environments. Furthermore, the approach developed in the present work could be extended to other polyelectrolytes and nanoparticles for fabricating novel multifunctional multilayer hollow microcapsules with aggregation-resistance performance in high ionic strength media.
be easily dispersed in water while the magnetic field is removed. This also showed that the superparamagnetic polyelectrolyte hybrid hollow microcapsules with magnetic-targeting function have significant potential for applications in the biomedical fields. The effect of ionic strength on the hollow microcapsules (CS/Fe3O4−CA)3 and (CS/Fe3O4−CA)3−CS−g-PEG was studied using the dynamic light scattering (DLS) technique. As shown in Figure 6, it can find that small molecule electrolyte
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AUTHOR INFORMATION
Corresponding Author
*Tel.: 86-931-8912516. Fax: 86-931-8912582. E-mail: pliu@ lzu.edu.cn. Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS This project was granted by financial support from the National Nature Science Foundation of China (Grant No. 20904017), the Program for New Century Excellent Talents in University (Grant No. NCET-09-0441), and the Fundamental Research Funds for the Central Universities (Grant No. lzujbky-2012k12).
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dx.doi.org/10.1021/ie301926m | Ind. Eng. Chem. Res. 2012, 51, 13875−13881
