A pH-sensitive graphene oxide composite hydrogelw

View Article Online / Journal Homepage / Table of Contents for this issue

COMMUNICATION

www.rsc.org/chemcomm | ChemComm

A pH-sensitive graphene oxide composite hydrogelw Hua Bai,ab Chun Li,a Xiaolin Wangb and Gaoquan Shi*a Received (in Cambridge, UK) 6th January 2010, Accepted 25th February 2010 First published as an Advance Article on the web 5th March 2010 DOI: 10.1039/c000051e

Downloaded by FORDHAM UNIVERSITY on 09 December 2012 Published on 05 March 2010 on http://pubs.rsc.org | doi:10.1039/C000051E

Graphene oxide/poly(vinyl alcohol) (GO/PVA) composite hydrogel was prepared and utilized for selective drug release at physiological pH. Graphene oxide (GO; Scheme 1) is a two-dimensional (2D) nanomaterial prepared from natural graphite and recently it has been widely used as a precursor of chemically converted graphene.1 GO can be easily exfoliated into monolayer sheets stably dispersed in water, mainly due to it bringing plenty of hydrophilic oxygenated functional groups.2 These groups also enable GO to be functionalized through covalent or non-covalent approaches.1 Therefore, GO is an important building block for synthesizing various functional materials.3 For example, thin films of GO sheets have been prepared by layer-by-layer deposition4 and the Langmuir–Blodgett (LB) technique.5 Recently, it was also reported that a small amount of GO could effectively reinforce poly(vinyl alcohol) (PVA) film, owing to the molecule-level dispersion of GO sheets in a PVA matrix and the strong interfacial interaction between these two components.6 However, to date, little attention has been paid to the solution properties of GO and the self-assembling behaviour of GO sheets. Herein, we report a novel nanocomposite hydrogel prepared from GO and PVA solutions. In this hydrogel, GO sheets form a network and PVA acts as a physical cross-linking agent. This is different from the case of classical nanocomposite hydrogels, in which nanomaterials usually provide cross-linking sites for the polymer gelators.7 Furthermore, the GO composite hydrogel is pH-sensitive; it is gellable in acidic media while undergoing gel–sol transition under alkaline conditions. Thus, it can be used for pH controlled selective drug release. GO was prepared by the modified Hummers’ method (see ESI, Fig. S1-2w).8 The procedures of preparing typical GO composite gel are described as follows. 642 mL GO dispersion (7.8 mg mL 1) were added into 358 mL PVA solution (containing 0.5–2.5 mg PVA), and the mixture was shaken violently for 10 s to form a gel. The formation of the gel was confirmed by a tube inversion method. To make the gelation process complete, the hydrogel was further treated by sonication for 20 min. The final hydrogels contain 5 mg mL 1 GO and 0.5–2.5 mg mL 1 PVA, indicating GO and PVA are a

so called ‘‘super gelator’’ with a critical gelation concentration o1 wt%.9 Hydrogel with GO concentration as low as 3 mg mL 1 can also be prepared, though its mechanical strength is weak (see ESI, Fig. S3w). The influence of cross-linking agent concentration on the gelation process was studied. Fig. 1 shows photographs of GO/PVA mixtures containing 5 mg mL 1 GO and PVA with various weight ratios to GO (rP/G). It is interesting to find that the gelation process strongly depends on rP/G. For PVA, both the lowest and the highest critical gelation concentrations were observed. A small amount of PVA (rP/G = 1 : 20) can significantly increase the viscosity of the GO solution (see ESI, Fig. S4w). However, for the GO/PVA mixtures with 5 mg mL 1 GO, the gelation can only occur as rP/G is in the range of 1 : 10 to 1 : 2. Further increasing PVA content will lead to a gel–sol transition. As rP/G = 1 : 1, the viscosity of the GO/PVA mixture is close to that of pure GO solution (see ESI, Fig. S4w). This phenomenon reveals that the interactions between GO and PVA components are different in the composites with low and high PVA contents. Pure GO and GO/PVA mixed solutions, as well as typical gels, were lyophilized for morphological study. The freezedried sample of 5 mg mL 1 GO maintained its original shape and volume, while the sample with 1 mg mL 1 GO exhibited an obvious shrinkage during lyophilization. These results imply that the suspension of 5 mg mL 1 GO is actually a semidiluted solution, and its GO volume fraction is large enough to make GO sheets contact with each other. Therefore, after removing water, a network of GO sheets was formed to keep the total volume of the sample. The network of GO sheets is clearly shown in Fig. 2A. All the samples with PVA components also maintained their volumes after lyophilization. The mixing of a small amount of PVA into GO solution (rP/G = 1 : 20) did not change the morphology of lyophilized sample and GO sheets were in extended states (Fig. 2B). A lyophilized gel with rP/G of 1 : 5 showed similar morphology (Fig. 2C). No PVA crystal was found in these two images, indicating that PVA chains were absorbed on the surfaces of GO sheets without phase separation on a large scale. However, if rP/G was increased to 1 : 1, the lyophilized sample showed a

a

Department of Chemistry and the Key Laboratory of Bio-organic Phosphorus Chemistry and Chemical Biology, Tsinghua University, 100084 Beijing, PR China. E-mail: [email protected]; Fax: +86 106 277 1149; Tel: +86 106 277 3743 b State Key Laboratory of Chemical Engineering, Department of Chemical Engineering, Tsinghua University, 100084 Beijing, PR China w Electronic supplementary information (ESI) available: Details of experiments, characterization of GO, rheological studies. See DOI: 10.1039/c000051e

2376 | Chem. Commun., 2010, 46, 2376–2378

Scheme 1 Structures of GO and PVA.

This journal is

c

The Royal Society of Chemistry 2010

View Article Online


Fig. 1 Photographs of GO/PVA mixtures with different content ratio (rP/G). From left to right, rP/G = 1 : 1, 1 : 1.5, 1 : 2, 1 : 5, 1 : 10, 1 : 20, 1 : 40.

different morphology (Fig. 2D). Many wire-like structures were observed, revealing that GO sheets were rolled up either in solution or during the lyophilization process. Fig. 3 illustrates the X-ray diffraction (XRD) patterns of lyophilized PVA, GO and GO/PVA composites. Pure GO shows a diffraction peak at 2y = 11.41, corresponding to an inter-planar spacing of 7.76 A˚.10 This result indicated that GO sheets aggregated after lyophilization. This is in agreement with the SEM image shown in Fig. 2A. Pure PVA exhibits a characteristic diffraction peak at 2y = 19.51, resulting from its (101) crystal planes.11 The XRD patterns of GO/PVA composites are different from those of pure GO and PVA, mainly due to the strong interaction between these two components. The XRD pattern of the sample with rP/G of 1 : 20 shows a diffraction peak (peak II) at 2y = 10.91. This is because a small amount of PVA absorbed on GO sheets induced a slight enlargement of GO inter-planar spacing from 7.76 to 8.11 A˚. When rP/G was increased to be higher than 1 : 10, a new peak at a small angle (2y = 9.21, 9.60 A˚, peak I) appeared, which further shifted to smaller angles with the increase of PVA content, and finally to 2y = 5.261 (16.8 A˚) as rP/G = 1 : 1. This new peak is attributed to PVA-spaced GO inter-planar spacing. When rP/G 4 1 : 2, only peak I was observed and peak II disappeared, indicating the absence of direct GO–GO packing mode in these composites and that GO sheets have been completely covered by PVA layers. Moreover, another new peak around 181 is observed (peak III), corresponding to a spacing of 4.9 A˚, which can be assigned to the spacing between PVA chains and GO sheets or the distance between PVA chains.

Fig. 2 SEM images of lyophilized 5 mg mL 1 GO (A) and GO/PVA blends (B–D); rP/G = 1 : 20 (B), 1 : 5 (C) or 1 : 1 (D). Scale bar: 5 mm.

This journal is

c


Fig. 3 XRD patterns of lyophilized PVA, GO and GO/PVA blends with various rP/G.

The SEM and XRD examination results described above provide a plausible explanation for the existence of both the lowest and the highest PVA critical gelation concentrations. Although GO nanosheets can contact with each other in their pure solution, the interaction force between them is weak. Therefore, the PVA component in the composite gel plays the role of cross-linking agent. The strong interaction between PVA and GO has been confirmed in previous reports,6 and hydrogen bonding is considered to be the dominant force. There are plenty of hydroxyl, epoxy and carboxyl groups on the surface of GO sheets,6 which can form hydrogen bonds with hydroxyl-rich PVA chains. One PVA chain can interact with two or more GO sheets, forming cross-linking sites. When the number of cross-linking sites is sufficiently high, a GO composite hydrogel is generated due to the formation of a GO network. However, when PVA content increased to a high value (rP/G 4 1 : 2), so many PVA chains were adsorbed on both surfaces of a single GO sheet that the cross-linking effect of PVA chains was greatly weakened. As a result, PVA-coated GO sheets behave like bulky PVA aggregates, while the gelation of pure PVA in water usually only occurs at much higher concentrations (B10 wt%).12 Another possible reason for the existence of highest critical gelation concentration of PVA is that GO sheets curled to wires in the composite solutions with high PVA concentrations (Fig. 2D). Therefore, the contact area between GO sheets was greatly reduced, which is unfavorable for the formation of hydrogel. It is believed that GO sheets can be dispersed into water because they bring negative charges on their surfaces, and the electrostatic repulsion (ER) prevents aggregation.13 These charges mainly originate from the carboxyl groups. Therefore, it is expected that the surface charge densities of GO sheets and the ER forces can be modulated by the pH value of the solution. As a result, the GO/PVA composite hydrogel is pH-sensitive. In fact, after addition of 10 mL 0.5 M NaOH aqueous solution to 1 mL composite hydrogel (rP/G = 1 : 10), the hydrogel decomposed quickly on dramatic shaking (Fig. 4). This is because the increase of pH value caused further ionization of carboxyl groups on GO sheets. Therefore, the ER forces between GO sheets increased because of the increase in their surface negative charge density. A gel–sol transition of the composite hydrogel occurred due to the lack of sufficient binding force between GO sheets. This pH-induced gel–sol transition is reversible and the solution Chem. Commun., 2010, 46, 2376–2378 | 2377

View Article Online


Fig. 4 Photographs of the pH-induced gel–sol transition.

of decomposed gel underwent a sol–gel transition upon addition of acid (Fig. 4). Furthermore, the acidic hydrogel is much stronger than its neutral counterpart (see ESI, Fig. S5w). This is mainly because the negative charges (carboxyl radicals) on GO sheets were reduced by acidification. As a result, the ER forces between GO sheets were weakened, leading to the formation of a more compact GO framework. An important application of hydrogel is delivering or controlled releasing of drugs.14 The GO/PVA composite hydrogel is biocompatible15 and pH-sensitive; therefore, it is a potential candidate for controlled drug release. Here, we chose vitamin B12 (VB12) as the model drug for evaluating the drug releasing ability of GO/PVA composite hydrogel. VB12 was successfully loaded into the hydrogel (rP/G = 1 : 10) by using PVA solution containing a certain amount of VB12 as one of the starting materials (see ESIw). Fig. 5 plots the drug release profiles of the GO/PVA hydrogel in phosphate buffer (PBS, 10 mM, pH = 7.4) and hydrochloric acid (pH = 1.7) solutions. From the curves, one can find that 84% VB12 molecules were diffused from the gel into neutral PBS solution after 42 h. However, in the acidic medium, only 51% VB12 can be released in the same period. Although having a fairly low gelator concentration (B0.55 wt%), the GO/PVA hydrogel was proved to be an efficient system for controlled drug release. In this case, the large 2D GO sheets behaved as permeability barriers and the diffusion paths of loaded drug molecules were increased greatly. In acidic solution, because GO sheets tended to form tightly packed aggregates, the diffusion of the loaded molecules was further limited. This pH-controlled drug release can be used to deliver and selectively release a drug in the intestine.16 It is known that some drugs may decompose in acidic medium, or cause

Fig. 5 Profiles of releasing VB12 from a GO/PVA composite hydrogel (rP/G = 1 : 10) in PBS (pH = 7.4) and HCl (pH = 1.7) solutions.

2378 | Chem. Commun., 2010, 46, 2376–2378

stomach discomfort; thus, this hydrogel can be used to deliver the drugs to the intestine (pH = 6.8–7.4) without much release in acidic gastric juice (pH = 1–2). In summary, we have demonstrated that GO sheets were able to form composite hydrogels with PVA. In these systems, GO sheets acted like 2D macromolecules. The formation of the hydrogels relies on the assembly of GO sheets and the cross-linking effect of PVA chains. The GO/PVA hydrogels exhibited pH-induced gel–sol transition and they can be used for loading and selectively releasing drugs at physiological pH. This study will provide a deeper understanding of the self-assembly behaviour of GO as a 2D molecular building block and inspire more novel designs of functional materials based on GO. This work was supported by the National Natural Science Foundation of China (50873052 and 20774056) and the China Postdoctoral Science Foundation (20090460027).

Notes and references 1 (a) S. Park and R. S. Ruoff, Nat. Nanotechnol., 2009, 4, 217–224; (b) H. Bai, Y. X. Xu, L. Zhao, C. Li and G. Q. Shi, Chem. Commun., 2009, 1667–1669. 2 W. W. Cai, R. D. Piner, F. J. Stadermann, S. Park, M. A. Shaibat, Y. Ishii, D. X. Yang, A. Velamakanni, S. J. An, M. Stoller, J. H. An, D. M. Chen and R. S. Ruoff, Science, 2008, 321, 1815–1817. 3 (a) S. Stankovich, D. A. Dikin, G. H. B. Dommett, K. M. Kohlhaas, E. J. Zimney, E. A. Stach, R. D. Piner, S. T. Nguyen and R. S. Ruoff, Nature, 2006, 442, 282–286; (b) Q. Su, S. Pang, V. Alijani, C. Li, X. Feng and K. Mu¨llen, Adv. Mater., 2009, 21, 3191–3195. 4 N. I. Kovtyukhova, P. J. Ollivier, B. R. Martin, T. E. Mallouk, S. A. Chizhik, E. V. Buzaneva and A. D. Gorchinskiy, Chem. Mater., 1999, 11, 771–778. 5 L. J. Cote, F. Kim and J. Huang, J. Am. Chem. Soc., 2009, 131, 1043–1049. 6 (a) J. Liang, Y. Huang, L. Zhang, Y. Wang, Y. Ma, T. Guo and Y. Chen, Adv. Funct. Mater., 2009, 19, 2297–2302; (b) Y. X. Xu, W. J. Hong, H. Bai, C. Li and G. Q. Shi, Carbon, 2009, 47, 3538–3543. 7 P. Schexnailder and G. Schmidt, Colloid Polym. Sci., 2009, 287, 1–11. 8 W. S. Hummers and R. E. Offeman, J. Am. Chem. Soc., 1958, 80, 1339. 9 (a) K. Murata, M. Aoki, T. Suzuki, T. Harada, H. Kawabata, T. Komori, F. Ohseto, K. Ueda and S. Shinkai, J. Am. Chem. Soc., 1994, 116, 6664–6676; (b) T. Klawonn, A. Gansauer, I. Winkler, T. Lauterbach, D. Franke, R. J. M. Nolte, M. C. Feiters, H. Borner, J. Hentschel and K. H. Dotz, Chem. Commun., 2007, 1894–1895. 10 Y. X. Xu, H. Bai, G. W. Lu, C. Li and G. Q. Shi, J. Am. Chem. Soc., 2008, 130, 5856–5857. 11 Y. Nishio and R. S. J. Manley, Macromolecules, 1988, 21, 1270–1277. 12 S. R. Stauffer and N. A. Peppas, Polymer, 1992, 33, 3932–3936. 13 D. Li, M. B. Muller, S. Gilje, R. B. Kaner and G. G. Wallace, Nat. Nanotechnol., 2008, 3, 101–105. 14 Y. Qiu and K. Park, Adv. Drug Delivery Rev., 2001, 53, 321–339. 15 Z. Liu, J. T. Robinson, X. M. Sun and H. J. Dai, J. Am. Chem. Soc., 2008, 130, 10876–10877. 16 L. C. Dong and A. S. Hoffman, J. Controlled Release, 1991, 15, 141–152.

This journal is

c
