J. Phys. Chem. B 2008, 112, 6315–6321
6315
Fabrication and Modulation of Magnetically Supramolecular Hydrogels Dong Ma and Li-Ming Zhang* Laboratory for Polymer Composite and Functional Materials, Institute of Optoelectronic and Functional Composite Materials, School of Chemistry and Chemical Engineering, Sun Yat-Sen (Zhongshan) UniVersity, Guangzhou 510275, China ReceiVed: December 7, 2007; ReVised Manuscript ReceiVed: February 27, 2008
For the fabrication of magnetically supramolecular hydrogels, the aqueous colloidal dispersion of magnetic iron oxide nanoparticles was first stabilized by an amphiphilic poly(ε-caprolactone)-poly(ethylene glycol) (PEG-PCL) block copolymer and then mixed with an aqueous solution of a cyclic oligosaccharide. Due to the host–guest interaction between the used block copolymer and the cyclic oligosaccharide in the aqueous mixed system, such a fabrication process could result in the formation of a novel hydrogel nanocomposite with superparamagnetic property, as confirmed by the analyses from rheology and X-ray diffraction as well as magnetization curve measurements. For the resultant magnetically supramolecular hydrogel, its formation kinetics and mechanical strength could be modulated by the amount of the used PEG-PCL block copolymer, the cyclic oligosaccharide, or the incorporated iron oxide nanoparticles. Introduction During the past few years, novel hydrogel nanocomposites containing functional metal nanoparticles embedded in crosslinked hydrogel networks have attracted increasing attention.1–7 This is due to their synergistic properties, unique functions, and numerous applications in biosensors, catalysts, switchable electronics, drug delivery devices, tissue repair, biomolecule separation, and purification. Among them, the hydrogel nanocomposites incorporated with magnetic nanoparticles have recently become the focus of broad research. For example, Mayer et al. 8 incorporated maghemite nanoparticles into the hybrid networks based on heteropolyanions and polyacrylamide and obtained a magnetic hydrogel nanocomposite with potential applications for biomaterials and optics. Goiti et al.9 prepared magnetic hydrogel nanocomposites by submitting an aqueous mixed system of poly(vinyl alcohol), poly(hydroxyethyl methacrylate), and magnetite nanoparticles to freezing-thawing cycles and investigated the effect of magnetic nanoparticles on the thermal properties of the hydrogels. Francois et al.10 incorporated an aqueous ferrofluid in scleroglucan hydrogels and prepared the magnetic hydrogels for the loading and in vitro release of a theophylline drug. Frimpong et al.11 fabricated the magnetically responsive hydrogel networks based on the composites of magnetic nanoparticles and temperature-responsive hydrogels, which showed a great promise as active components of microscale and nanoscale biomedical devices. Very recently, our group12 synthesized the magnetic hydrogel nanocomposites by the in situ embedding of magnetic iron oxide nanoparticles into the porous chitosan hydrogel networks and explored their potential application in the magnetically assisted bioseparation for bovine serum albumin. Up to now, the fabrication methods for magnetic hydrogel nanocomposites involved mainly the incorporation of magnetic nanoparticles into the hydrogel matrix by mixing, simultaneous formation of both the hydrogel matrix and magnetic nanopar* To whom correspondence should be addressed. E-mail: ceszhlm@ mail.sysu.edu.cn.
ticles in the reaction system, as well as the in situ formation of magnetic nanoparticles in the preformed hydrogel network. Although commonly used, these methods are often limited in scope. Therefore, the development of facile and effective preparation strategies toward such functional hydrogel materials is a meaningful challenge. In this work, we demonstrate a novel route for the construction of magnetic hydrogel nanocomposites. In our stragegy, a biocompatible poly(ethylene glycol)- poly(ε-caprolactone) (PEG-PCL) block copolymer with amphiphilic character was first used as the stabilizing agent for the preparation of colloidally stable ferrofluid (I) containing iron oxide (Fe3O4) nanoparticles and subsequently used as the guest molecule for the inclusion complexation with a cyclic oligosaccharide host molecule, R-cyclodextrin (II), in an aqueous mixed system of I and II. As a result, a novel magnetically supramolecular hydrogel with adjustable gelation time, mechanical strength, and magnetic property could be fabricated. In recent years, the supramolecularstructured hydrogels,13–15 which resulted from the host–guest interactions of cyclodextrins with some polymers, and magnetic Fe3O4 nanoparticles16–18 have been widely studied and have shown many promising applications in biotechnology and bioengineering. Thus, our present attempt to combine magnetic Fe3O4 nanoparticles with supramolecular-structured hydrogels may provide a new possibility to modulate the physical and chemical properties of functional hydrogel nanocomposites, which will extend their applications in many areas. Experimental Section Materials. Iron(II) chloride tetrahydrate (99%) and iron(III) chloride hexahydrate (98%) were purchased from Guangzhou chemical company (China). R-Cyclodextrin (Sigma, U.S.A.) was used after drying under vacuum at 65 °C for 24 h. ε-Caprolactone (ε-CL) was purchased also from Sigma and was dried over CaH2 for 24 h and distilled prior to use. Poly(ethylene glycol) (PEG) (Mn ) 10 kDa) was provided by Shanghai Chemical Company in China and used after drying under vacuum at 95 °C for 48 h. Stannous octoate (Sigma, USA) was used as received. R-CD (Sigma, U.S.A.) was used after drying in a
10.1021/jp7115627 CCC: $40.75 2008 American Chemical Society Published on Web 04/24/2008
6316 J. Phys. Chem. B, Vol. 112, No. 20, 2008
Figure 1. H1 NMR spectrum of the amphiphilic PEG-PCL-10K block copolymer used in this study (CDCL3).
vacuum at 65 °C for 24 h. All other chemicals used were analytical grade and used without further purification.The water used was Milli-Q ultrapure water. PreparationandCharacterizationofAmphiphilicPEG-PCL Block Copolymer (PEG-PCL-10K). A poly(ε-caprolactone) (PCL) segment was attached to both ends of PEG to obtain the amphiphilic PCL–PEG block copolymer. Briefly, a roundbottom flask with a stopcock was heated under reduced pressure to remove the moisture. After cooling to room temperature, argon was introduced into the falsk. Following this, ε-CL (24.0 mmol) and PEG (1.0 mmol) were added, and the mixture was heated with continuous stirring to produce a well-mixed molten phase. The mixture was then cooled, and stannous octoate (0.2 wt % of ε-CL) was added to the flask under an argon environment. The mixture was degassed and then heated to 130°. After stirring for 16 h, the content was cooled to room temperature. The product was dissovled in methylene chloride and then precipitated in ethyl ether. The block copolymer was filtered and dried overnight under vacuum, with a 92% yield. Figure 1 shows the H1 NMR spectrum of the block copolymer sample (PEG-PCL-10K). The peaks at 1.39, 1.65, 2.31, and 4.06 ppm are assigned to methylene protons of -(CH2)3-, -OCCH2-, and -CH2OOC- in PCL units, respectively. The sharp single peak at 3.64 ppm is attributed to the methylene protons of homosequences of the PEG oxyethylene units. The very weak peak at 4.23 ppm is attributed to the methylene proton of the PEG end unit. These analyses confirm the successful synthesis of the amphiphilic PCL-PEG block copolymer.19 The number of PEG units in the block copolymer was determined to be 227 (Mn/44), and the number of PCL units in the block copolymer was determined to be 24 by the H1 NMR integral ratio.19 Preparation, Dispersion, and Characterization of Magnetic Nanoparticles. Magnetic Fe3O4 nanoparticles were prepared by coprecipitating iron(II) and iron(III) in an alkaline solution and then treating it under hydrothermal conditions. At first, a 0.30% aqueous iron(II) chloride tetrahydrate dispersion and a 0.85% iron(III) chloride hexahydrate dispersion were thoroughly mixed and added to 8.0 mol/L NaOH under continuous stirring at room temperature. Then, the reaction mixture was heated at 80 °C for 30 min, and the medium pH was maintained at 10 by the addition of aqueous NaOH during the reaction. After removing impurity ions such as chlorides, the resulting magnetic nanoparticles were washed with distilled water and ethanol and dried in a vacuum oven at 70 °C. For
Ma and Zhang the dispersion of as-obtained Fe3O4 nanoparticles in an aqueous solution of PEG-PCL-10K, a required amount of PEG-PCL10K was dissolved in water to form a transparent solution and then mixed with an aqueous suspension of the Fe3O4 nanoparticles. The mixture was sonicated for 30 min, resulting in a homogeneously black solution. For the Fe3O4 nanoparticles in aqueous dispersions with and without PEG-PCL-10K, their size and morphology were observed by a JEM-2010HR transmission electron microscope (TEM, Japan), and their colloidal stability in aqueous medium was evaluated on the basis of the measurement for their optical absorbance with a UV–vis spectrophotometry (UV-3150, Shimadzu, Japan) set at a wavelength of 550 nm. Square glass cuvettes with a path length of 1 cm were used. Formation of Magnetic Hydrogel Nanocomposites and Their Characterization. A required amount of aqueous R-CD solution was added into an aqueous dispersion of magnetic nanoparticles and PEG-PCL-10K. The mixture system was thoroughly stirred and set aside at ambient temperature. A gelation occurred to result in a physical network hybrized with Fe3O4 nanoparticles due to the supramolecular self-assembly between R-CD and PEG-PCL-10K. For the characterization of the hydrogel samples, X-ray diffraction measurements were performed by using a Rigaku D/max-2200 type X-ray diffractometer. The radiation source used was Ni-filtered Cu KR radiation with a wavelength of 0.154 nm. The voltage was set to 40 kV, and the current was set to 40 mA.The proportional counter detector collected data at a rate of 2θ ) 1° min-1 over the range 2θ ) 5–75°. The gelation process was monitored by the rheological method,20 and the dynamic storage modulus (G′) and loss modulus (G′′) of the resulting hydrogel sample were measured at 25 °C by means of an advanced rheometric extended system (ARES, TA Co.) in oscillatory mode with a cone-and-plate geometry (cone diameter, 25 mm; angle, 1°). To ensure the rheological measurements within a linear viscoelastic region, a dynamic strain sweep was conducted prior to the frequency sweep, and the corresponding strain was determined to be 1.0%. For the investigation of the hydrogel strength, the storage modulus of the resultant hydrogel sample was measured when the gelled system was aged for 24 h at room temperature in order to finish the gelation. The magnetic property was evaluated using a Xl-7 magnetic property measurement system (U.S.A.) with a maximum magnetic field of 7 T and a sensibility of 10-6 emu at 300 K. The thermogravimetric (TG) analyses were conducted by using a NetzschTG-209 thermogravimetry analyzer in nitrogen at a purge rate of 50 mL · min-1. The heating rate was set as 10 °C/ min, and the scanning temperature was in the range from 20 to 700 °C. The differential scanning calorimetry (DSC) curves were measured by using a Perkin-Elmer DSC-7 calorimeter (U.S.A.) for the hydrogel sample at a heating rate of 3 °C · min-1 under a 25 mL · min-1 nitrogen flow. Results and Discussion The stabilization for an aqueous dispersion of magnetic Fe3O4 nanoparticles is important for the fabrication of a magnetically supramolecular hydrogel. It is known that the aqueous dispersion of magnetite nanoparticles could be stabilized by amphiphilic copolymers or polymeric surfactants.21–23 In this study, we synthesized a water-soluble amphiphilic PEG-PCL block copolymer, namely, PEG-PCL-10K, for this purpose. It is expected that the used PEG-PCL-10K can act not only as the
Magnetically Supramolecular Hydrogels
Figure 2. The relative optical absorbance (A/A0) as a function of the setting time for aqueous 0.5 wt % Fe3O4 nanoparticle dispersions with and without amphiphilic PEG-PCL-10K block copolymer.
effective guest molecule for the supramolecular self-assembly but also as the effective stabilizing agent for colloidal magnetic dispersion. When Fe3O4 nanoparticles were dispersed in an aqueous solution of PEG-PCL-10K by ultrasonication, we found that a macroscopically homogeneous dispersion could be obtained. Figure 2 gives the relative optical absorbance (A/A0) as a function of the setting time for aqueous 0.5 wt % Fe3O4 nanoparticle dispersions with and without PEG-PCL-10K. As shown, the A/A0 value has an obvious decrease in the absence of PEG-PCL-10K. This may be attributed to the strong hydrophobic interaction between the naked magnetic particles,18 which makes these particles easier to agglomerate and thus leads to an obvious decrease of the A/A0 value. In the cases of 1.0, 2.5, and 5.0 wt % PEG-PCL-10K, however, the A/A0 values of the magnetic dispersion system have only a little change, showing a good colloidal stability. Particularly, this became obvious when 5.0 wt % PEG-PCL-10K was used. It seems that an increase of the PEG-PCL-10K concentration results in a better stabilization for the aqueous dispersion of magnetic Fe3O4 nanoparticles. These results may be attributed to the surface modification of PEG-PCL-10K on the Fe3O4 nanoparticles, which shields the hydrophobic interactions between the magnetic nanoparticles. Figures 3 shows the typical TEM images and corresponding histograms for aqueous Fe3O4 nanoparticle dispersions without and with 1.0 wt % PEG-PCL-10K. Although the sample preparation for SEM observation may induce some aggregation of the magnetic particles since the particles must be deposited on a grid, the aggregation degree of the magnetic particles in the presence of PEG-PCL-10K is far smaller than that of the magnetic particles in the absence of PEG-PCL-10K. In addition, the aggregate size was estimated by measuring the lengths of the 80 particles within different regions of a given TEM grid containing the dispersion. As a result, the aggregate size in an aqueous magnetic dispersion with 1.0 wt % PEG-PCL-10K was found to range from 11.0 to 19.0 nm, while the aggregate size in an aqueous magnetic dispersion without PEG-PCL-10K was found to range from 11.0 to 24.0 nm, showing that the former has a narrow size distribution. These results confirm further the stabilization of PEG-PCL-10K for aqueous dispersion of magnetic Fe3O4 nanoparticles. For the resultant colloidal magnetic dispersion stabilized by PEG-PCL-10K, it is interesting to find that a gelation could occur when it is mixed with an aqueous R-CD solution. In some
J. Phys. Chem. B, Vol. 112, No. 20, 2008 6317 cases, the invertible hydrogel composite sample containing Fe3O4 nanoparticles could be obtained, as shown in Figure 4. This phenomenon may be attributed to the inclusion complex formation between PEG-PCL-10K and R-CD, which results in a supramolecular-structured hydrogel. To confirm this, X-ray diffraction (XRD) measurements were conducted for pure Fe3O4 nanoparticles, pure hydrogel resulting from 5.0 wt % PEG-PCL10K and 4.0 wt % R-CD, and magnetic hydrogel nanocomposites (MHNs). These MHN samples were obtained from 4.0 wt % R-CD, 0.5 wt % Fe3O4 nanoparticles, and different concentrations of PEG-PCL-10K, namely, MHN-1 for 1.0 wt % PEG-PCL-10K, MHN-2 for 2.5 wt % PEG-PCL-10K, and MHN-3 for 5.0 wt % PEG-PCL-10K. From the XRD patterns shown in Figure 5, it was found that two characteristic diffraction peaks at 2θ ) 19.2 and 23.3°, which represent the channel-type structure of the R-CD and PEG complex,24–26 were observed not only in the diffractogram of the pure hydrogel sample without Fe3O4 nanoparticles but also in the diffractograms of three MHN samples. Moreover, the characteristics peaks of pure Fe3O4 nanoparticles at 2θ ) 30.1, 35.9, 43.1, 57.0, and 62.6 °, which could be marked, respectively, by their indices (220), (311), (400), (511), and (440),27 were also observed in the diffractograms of three MHN samples. These results demonstrate that the inclusion complexation has occurred in such a hydrogel hybrid system, regardless of the incorporated Fe3O4 nanoparticles. Meanwhile, the hybridization process developed in this study does not result in the phase change of magnetic iron oxide nanoparticles, which would be favorable for keeping the magnetic function. By using the Scherrer equation and fitting the characteristic peak at an angle of 2θ ) 35.9° (the (311) diffraction plane) to a pseudo-Voigt function,28,29 the average aggregate size of the embedded Fe3O4 nanoparticles was estimated to be 12.2 nm in the case of 1.0% PEG-PCL-10K, 11.8 nm in the case of 2.5% PEG-PCL-10K, and 10.7 nm in the case of 5.0% PEG-PCL-10K. It seems that a higher concentration of PEG-PCL-10K is more favorable for the stabilization of magnetic nanoparticles. Meanwhile, a small value (
