Silica Nanoparticle-Mediated Solution-Phase Separation to Highly

Oct 16, 2014 - Fundamental Science on Radioactive Geology and Exploration Technology Laboratory, School of Chemistry, Biology and Materials Science, ...
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Silica Nanoparticle-Mediated Solution-Phase Separation to Highly Porous Polylactide Membranes Qingxian Liu, Peng Zhang, Bing Na,* Ruihua Lv, and Renping Tian Fundamental Science on Radioactive Geology and Exploration Technology Laboratory, School of Chemistry, Biology and Materials Science, East China Institute of Technology, No. 418 Guanglan Road, Nanchang 330013, People’s Republic of China ABSTRACT: Immersion precipitation of polylactide (PLA)/ chloroform solutions in methanol yields membranes with lack of pore interconnectivity. In contrast, incorporation of silica nanoparticles (NPs) in the solutions promotes pore interconnectivity throughout the membranes. The selective association of silica NPs with chloroform upon phase separation significantly prevents the contraction caused by the formation of the PLA matrix, thus responsible for pore interconnectivity. Besides, pore size can be tailored by the PLA concentration in the solutions and the polarity of silica NPs. This study demonstrates that silica NPs can mediate solution-phase separation during immersion precipitation, which provides a facile route to achieve highly porous membranes.

1. INTRODUCTION Polylactide (PLA) is widely used as porous scaffolds in many applications because of its biocompatibility and biodegradability.1−5 The main concerns regarding porous scaffolds are in the control of pore size and interconnectivity among pores. To date, several techniques have been developed to fabricate porous PLA scaffolds, including phase separation, particulate leaching, gas foaming, electrospinning, and so on.6−8 Of them, solution-phase separation induced by a nonsolvent during immersion precipitation usually results in membranes with dense skins and isolated pores in the bulk.9 It makes the membranes obtained by immersion precipitation not suitable for porous scaffolds. Nanoparticles (NPs) are frequently reported to control the morphology of polymer blends and block copolymers.10−15 For instance, NPs act as compatibilizers for immiscible polymer blends to retard the coarsening process during phase separation or drive assembly of block copolymer into ordered structures. It is believed that morphological variation arises from the interactions between NPs and components. Following these studies, it is natural to expect that NPs could affect phase separation of a polymer solution during immersion precipitation and thus the morphology of resulted membranes. As a matter of fact, incorporation of NPs in the solutions alters to some extent the morphology of membranes.16 Unfortunately, dense skins and poor interconnectivity among pores also prevail in the membranes. Here we demonstrate that the presence of silica NPs in the PLA/chloroform solutions significantly promotes the formation of highly porous membranes upon immersion precipitation in methanol. It arises from the fact that silica NPs mediate solution-phase separation due to interactions and association of silica NPs with chloroform, which opens a new way to produce highly porous membranes by immersion precipitation. © 2014 American Chemical Society

2. EXPERIMENTAL SECTION Materials. Poly(L-lactide) (abbreviated as PLA), purchased from Natureworks, USA, had a Mn and Mw of 123 and 210 kg/ mol, respectively. It had a glass-transition temperature of ∼60 °C and a melting point of ∼168 °C. Two kinds of fumed silica NPs were supplied by Evonik Industries, Germany: one was hydrophobic with a surface area of 170 m2/g and average primary particle diameter of 12 nm, the other was hydrophilic with a surface area of 380 m2/g and average primary particle diameter of 7 nm. Hydroxyapatite NPs, provided by Beijing Dk Nano technology, China, had a surface area of 50 m2/g and average diameter of 20 nm. The ionic liquid, 1-butyl-3methylimidazolium tetrafluoroborate [BMIM] BF4 , was obtained from Lanzhou institute of Chemical Physics, China, and used as received. Fabrication of Membranes. Membranes were produced by immersion precipitation of PLA/chloroform/silica NPs solutions in a large amount of methanol at 4 °C. The concentration of PLA in the solutions was 40 and 100 mg/mL, respectively, and the content of silica NPs ranged between 0 and 50 wt % (based on the weight of PLA). To remove silica NPs, we ultrasonically washed the resulted membranes in ethanol for 30 min (for ones with large pores obtained from the solutions with a concentration of 40 mg/mL) or immersed them in a 2.3% HF aqueous solution overnight (for ones with small pores obtained from the solutions with a concentration of 100 mg/mL). Characterizations. The morphology of membranes was probed by a Nova NanoSEM 450 scanning electron microscope (SEM). The cross-section of membranes was obtained by Received: September 11, 2014 Revised: October 10, 2014 Published: October 16, 2014 25620

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cryofracture in liquid nitrogen. A thin gold layer was sputtered prior to SEM measurements. Relative viscosity of chloroform/ silica NPs mixtures was determined by an Ubbelohde viscometer at 25 °C. Fourier transform infrared spectroscopy (FTIR) measurements on silica NPs were conducted by a Thermo Nicolet FTIR spectrometer with a resolution of 4 cm−1 at room temperature. To measure porosity and ionic conductivity, we immersed porous membranes in the ionic liquid [BMIM] BF4 for 4 h at room temperature. Afterward, the porous membranes were taken out and wiped by filter papers to remove the additional ionic liquid on the surface. The porosity was calculated from the volume of absorbed ionic liquid (i.e., pore volume) and the volume of the solid part. For ionic conductivity measurements, the porous membranes containing the ionic liquid were sandwiched between a pair of stainlesssteel electrodes covered with Teflon casing. The impedance spectra were obtained by the AC complex impedance technique over the frequency range from 1 Hz to 115 kHz using a CS310 electrochemical workstation at room temperature. The resistance was deduced from the high-frequency intercept on the real axis of the impedance spectra. The ionic conductivity was calculated from the resistance with knowledge of sample thickness and the area of the electrodes. Figure 2. SEM micrographs revealing morphology (a−c) on the surface and (a′−c′) in the cross-section of the membranes obtained from the solutions containing hydrophobic silica NPs: (a,a′) 10 wt %, (b,b′) 30 wt %, (c,c′) 50 wt %. The PLA concentration in the solutions is 40 mg/mL.

3. RESULTS AND DISCUSSION Figure 1 shows the morphology of membranes prepared by immersion precipitation of PLA/chloroform solutions with a

contraction caused by the formation of the PLA matrix. Therefore, pores are produced and silica NPs are left around the pores after evaporation of solvents. A similar situation is also encountered in the inner part of the membranes where silica NPs are separated from the PLA matrix (Figure 2a′−c′). Moreover, pores seem to be highly interconnected, while high content of silica NPs is incorporated in the solutions. To confirm this, we ultrasonically washed membranes from the solutions with 50 wt % hydrophobic silica NPs in ethanol, and the resulting morphology is given in Figure 3. As a matter of fact, pores are penetrated throughout the

Figure 1. SEM micrographs revealing morphology (a) on the surface and (b) in the cross-section of the membranes obtained from PLA/ chloroform solutions with a PLA concentration of 40 mg/mL.

PLA concentration of 40 mg/mL. Only a few pores are generated on the surface of the membranes (Figure 1a). It corresponds to rapid phase separation induced by methanol and thus severe contraction of the PLA component during immersion precipitation. Once the relatively dense skins are formed, phase separation in the inner part becomes slow due to the barrier effect from skins, and thus large pores are produced inside the membranes. Moreover, interconnectivity among pores is very poor (Figure 1b). It is a common observation in the membranes generated by immersion precipitation of polymer solutions in a nonsolvent.9,17,18 However, the previous situations are significantly altered while hydrophobic silica NPs are incorporated in the PLA/ chloroform solutions with a PLA concentration of 40 mg/mL. As depicted in Figure 2a−c, surface porosity of the membranes is increased with the content of silica NPs in the solutions, and highly porous surface is achieved from the solution with 50 wt % silica NPs. A close inspection reveals that in all cases silica NPs are located around the pores and not embedded in the PLA matrix. It suggests that during phase separation silica NPs are selectively associated with chloroform rather than with the PLA component. Moreover, it is expected that chloroformcontaining silica NPs can, to a large extent, withstand the

Figure 3. SEM micrographs revealing morphology (a) on the surface and (b) in the cross-section of the membranes after removal of hydrophobic silica NPs. The PLA concentration in the solutions is 40 mg/mL and the content of hydrophobic silica NPs is 50 wt %.

membranes and pore interconnectivity is exhibited. It is further verified by the complete removal of silica NPs from the membranes upon ultrasonic washing. In other words, without pore interconnectivity, silica NPs could not be washed out from the inner part of the membranes. Figure 4 gives morphology of the membranes from the solution containing 50 wt % hydrophobic silica NPs with a PLA concentration of 100 mg/mL. For comparison, those from the solutions without silica NPs are included. Similarly, highly 25621

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Figure 4. SEM micrographs revealing morphology (a,b) on the surface and (a′,b′) in the cross-section of the membranes after removal of hydrophobic silica NPs. The content of hydrophobic silica NPs is (a,a′) 0 and (b,b′) 50 wt %, respectively, and the PLA concentration in the solutions is 100 mg/mL.

Figure 6. Photographs revealing penetration of methanol dyed by rhodamine B from top (upper) to bottom (lower) surfaces of the membranes obtained from the solutions with a PLA concentration of 100 mg/mL: (a) without silica NPs, (b) with 50 wt % hydrophobic silica NPs, and (c) with 50 wt % hydrophilic silica NPs. The concentration of rhodamine B in methanol is 20 mg/mL.

interconnected pores are induced by silica NPs throughout the PLA membranes. The difference is that pore size is much smaller than that in the membranes from the solutions with lower PLA concentration (Figure 3). It corresponds to more PLA chains available in the solutions with higher PLA concentration to yield denser matrix upon phase separation. This is well illustrated by the very dense surface of membranes obtained from the PLA/chloroform solution without silica NPs (Figure 4 a). Incorporation of hydrophilic silica NPs in the solutions also benefits the generation of highly interconnected pores in the membranes, as shown by SEM micrographs in Figure 5. Of note, the membranes were prepared from the solutions containing 50 wt % hydrophilic silica NPs with a PLA concentration of 40 and 100 mg/mL, respectively. To further confirm pore interconnectivity throughout the membranes, we placed a small drop of methanol dyed by rhodamine B on the top surface of the membranes obtained from the solutions with a PLA concentration of 100 mg/mL. Figure 6 shows the corresponding photographs of top and

bottom surfaces of the membranes after dropping the dyed methanol. The droplet instantaneously penetrated the membranes fabricated from the solutions containing 50 wt % hydrophobic or hydrophilic silica NPs because of highly interconnected pores. As a result, the trace of rhodamine B appeared on the bottom surface of the membranes. In contrast, the droplet stayed on the top surface of the membranes with dense skins prepared from the solutions without silica NPs, and no trace of rhodamine B was observed on the bottom surface of the membranes. As given in Table 1, in addition, significant Table 1. Properties of the Membranes Obtained from Solutions with A PLA Concentration of 100 mg/mL without and with 50 wt % Silica NPs sample

uptake of the ionic liquid (wt %)

porosity (%)

ionic conductivity (mS/cm)

without silica NPs hydrophobic silica NPs hydrophilic silica NPs

13.1 337.8 352.2

78.6 79.3

1.05 1.17

uptake of the ionic liquid is exhibited by highly porous membranes. As a comparison, the membranes prepared from the solutions without silica NPs have only a small uptake of the ionic liquid due to dense skins and poor interconnectivity among pores. The deduced porosity is 78.6 and 79.3% for the membranes obtained from the solutions containing 50 wt % hydrophobic and hydrophilic silica NPs, respectively. Moreover, high ionic conductivity up to 1.17 mS/cm is observed for highly porous membranes filled with the ionic liquid. It again indicates that pore interconnectivity throughout the membranes is induced by hydrophobic and hydrophilic silica NPs. Note that the porosity and ionic conductivity for the membranes from the solutions without silica NPs are not available because of very low uptake of the ionic liquid. As compared with the hydrophobic counterpart, incorporation of hydrophilic silica NPs creates much larger pores in the membranes, especially from the solutions with a PLA concentration of 40 mg/mL. As previously mentioned, generation of highly interconnected pores in the membranes

Figure 5. SEM micrographs revealing morphology (a,b) on the surface and (a′,b′) in the cross-section of the membranes after removal of hydrophilic silica NPs. The PLA concentration is (a,a′) 40 and (b,b′) 100 mg/mL, respectively, and the content of hydrophilic silica NPs is 50 wt %. 25622

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normalized according to the absorbance of the IR band around 1100 cm−1 that is contributed by the Si−O stretching vibration. The above results clearly demonstrate that silica NPs promote highly interconnected pores throughout the membranes via immersion precipitation. It arises from the selective association of silica NPs with chloroform upon phase separation as well as thickening effect of silica NPs in chloroform. Therefore, contraction of the PLA component during solidification can be suppressed to a large extent, resulting in highly interconnected pores in the membranes. After the removal of chloroform and silica NPs, highly porous membranes are thus obtained. The processes related to the formation of highly porous membranes induced by silica NPs are schematically shown in Figure 8. In a word, silica NPs in this case play a vital role in mediating phase separation of PLA/chloroform/silica NPs solutions, similar to that observed in the immiscible polymer blends or block copolymers in the presence of NPs.10−15 As argued in the pioneering studies, the effect of NPs on the phase separation is originated from the interactions between NPs and components. Herein, it relies on the interactions and association between silica NPs and chloroform in the solutions. If not, highly porous membranes could be not achieved by immersion precipitation. As an example, hydroxyapatite NPs were adopted to fabricate PLA membranes under the identical conditions. Figure 9

by immersion precipitation arises from the selective association of silica NPs with chloroform during phase separation. Therefore, larger pores induced by hydrophilic silica NPs should be related to stronger thickening effects of hydrophilic silica NPs in chloroform. As illustrated by relative viscosity in Figure 7a, at the same loadings chloroform containing

Figure 7. (a) Relative viscosity of chloroform/silica NPs mixtures with respect to chloroform and (b) FTIR spectra of hydrophobic and hydrophilic silica NPs.

Figure 9. SEM micrographs revealing morphology (a) on the surface and (b) in the cross-section of the membranes obtained from the solutions containing 50 wt % hydroxyapatite NPs. The PLA concentration in the solutions is 100 mg/mL.

hydrophilic silica NPs exhibits higher relative viscosity than that containing the hydrophobic counterpart. Note that the concentration of silica NPs in chloroform is the same as that in the PLA/chloroform/silica NPs solutions with a PLA concentration of 40 mg/mL. It mostly arises from more interactions of hydrophilic silica NPs with more hydroxyl groups in chloroform. As shown in Figure 7b, a significant IR absorption band in the wavenumber range between 3000 and 3700 cm−1 that is assigned to the stretching vibration of hydroxyl groups is observed for hydrophilic silica NPs. Of note, for comparison, the absorbance of hydroxyl groups is

presents morphology of the membranes from the solutions containing 50 wt % hydroxyapatite NPs (based on the weight of PLA) with a PLA concentration of 100 mg/mL. Different from those induced by silica NPs, the membranes obtained from the solutions containing hydroxyapatite NPs exhibit dense surfaces and isolated pores in the inner part. This morphology is very similar to that of the membranes produced from PLA/ chloroform solutions (Figure 4a,a′). Moreover, hydroxyapatite NPs are mostly embedded in the PLA matrix, indicating that

Figure 8. Schematic diagram of silica NPs-mediated solution phase separation to highly porous PLA membranes. 25623

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Program of Natural Science Foundation of Jiangxi, China (No. 20133ACB21006) and the Program for Young Scientists of Jiangxi Province (No. 20112BCB23023).

during phase separation hydroxyapatite NPs are mainly associated with the PLA component rather than with chloroform. It arises from poor interactions and association between hydroxyapatite NPs and chloroform. As shown in Figure 10, hydroxyapatite NPs are insoluble in chloroform, and

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Figure 10. Photographs of chloroform/NPs mixtures with a NPs concentration of 20 mg/mL: (a) hydroxyapatite, (b) hydrophobic silica, and (c) hydrophilic silica.

white precipitates are observed at the bottom of the vial, whereas both kinds of silica NPs exhibit good solubility in chloroform to form transparent solutions. Finally, it should be noted that the role played by silica NPs in fabricating highly porous membranes is different from that by particles as regarding particulate leaching technique. In the latter technique,3,19,20 dense membranes containing particles are first produced by solvent evaporation of solutions. Afterward, particles are leached from the dense membranes to generate pores by another solvent. Pore interconnectivity is determined by the contact among particles in the dense membranes, and pore size is controlled by particle size. In this case, however, pore interconnectivity in the membranes is achieved by silica NP-mediated phase separation of the solutions rather than by the removal of silica NPs, and pore size is dependent on the PLA concentration in the solutions and the polarity of silica NPs, irrespective of the size of silica NPs.

4. CONCLUSIONS Highly porous PLA membranes are produced by immersion precipitation of PLA/chloroform solutions with the aid of silica NPs. It arises from the selective association of silica NPs with chloroform during phase separation and the related thickening effects of silica NPs in chloroform. In addition, pore size of the membranes can be tuned by the PLA concentration in the solutions as well as the polarity of silica NPs. This study provides a facile route to achieve highly porous PLA membranes that could be used as scaffolds for active compounds.

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REFERENCES

AUTHOR INFORMATION

Corresponding Author

*Fax: +86 791 83897982. E-mail: [email protected], bingnash@ 163.com. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work is financially supported by the National Natural Science Foundation of China (No. 21364001), the Major 25624

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(20) Watanabe, J.; Eriguchi, T.; Ishihara, K. Stereocomplex Formation by Enantiomeric Poly (lactic acid) Graft-Type Phospholipid Polymers for Tissue Engineering. Biomacromolecules 2002, 3, 1109−1114.

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