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Article history: In order to find new composite materials for the controlled release of drugs, a series of novel pH sensitive
Received 28 April 2013 konjac glucomannan/sodium alginate (KGM/SA) and KGM/SA/graphene oxide (KGM/SA/GO) hydrogels
Received in revised form 31 August 2013 were prepared, using GO as a drug-binding effector for anticancer drug loading and release. The hydro-
Accepted 3 September 2013
gels were characterized using Fourier transform infrared spectroscopy (FTIR), and scanning electron
Available online xxx
microscopy (SEM). The effects of component ratio and pH on the swelling properties of hydrogels were
studied. The release amount of 5-fluorouracil (5-FU) incorporated into KGM/SA/GO-3 hydrogels was
Keywords:
about 38.02% at pH 1.2 and 84.19% at pH 6.8 after 6 h and 12 h, respectively. Therefore, the release rate of
pH sensitive
Drug-binding effector
5-FU from the functionalized KGM/SA using GO could be effectively controlled, Go has a great potential
Graphene oxide to be a promising drug-binding effector for hydrogel functionalization in drug delivery.
Konjac glucomannan © 2013 Elsevier B.V. All rights reserved.
0927-7765/$ – see front matter © 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.colsurfb.2013.09.009
224 J. Wang et al. / Colloids and Surfaces B: Biointerfaces 113 (2014) 223–229
Table 1
Feed composition for the preparation of KGM, KGM/SA, and KGM/SA/GO hydrogels and drug loading (EEs).
Sample KGM (g) SA (g) GO (g) H2 O (ml) Ca(OH)2 (ml) EEs (%)
Jin et al. reported the pH-controlled release of 5-FU from 5-FU/- total polysaccharide concentration at 1% (w/v). Then, a Ca(OH)2
cyclodextrin complex intercalated in double layered hydroxide suspension (10 mL) was added into the beaker and the speed of
[20]. Jin demonstrated a proof-of-concept approach for construc- mechanical was increased to 800 rpm. After 10 min, the beaker was
ting a novel micelle-drug conjugate system for the photo-triggered transferred to an oil bath and the mixture was heated at 90 ◦ C for
release of 5-FU under physiological conditions [21]. However, the 6 h for deacetylation and crosslinking. The obtained hydrogels were
degradation of carriers produced unwanted toxic effects [22]. washed five times with aqueous HCl solution (10:1, v/v) followed
In this study, KGM was used as the matrix to prepare more stable by five washings with deionized water to remove small molecules
intelligent hydrogels, using SA as the pH sensitive agent and GO as and residual base, and then dried to a constant weight at 40 ◦ C and
drug binding effector. Furthermore, the release profiles of a model stored until further used. The codes of all hydrogels are listed in
drug, 5-FU, from the test hydrogels were studied in simulated gas- Table 1.
tric and intestinal pH media. Moreover, the interaction between
5-FU and GO has been investigated by UV–vis spectroscopy. 2.4. Preparation of KGM/SA/GO nanocomposite hydrogels
2.8. Characterization
Scheme 1. The possible mechanism of the gelation of KGM, KGM/SA, and KGM/SA/GO hydrogels.
Fig. 2. SEM images of neat KGM (a and d), KGM/SA-3 (b and e), and KGM/SA/GO-3 (c and f) hydrogels.
The swelling ratio of most hydrogels at pH 6.8 increases to a 3.3. 5-FU loading
higher extent than that at pH 1.2 with increasing time as shown
in Fig. 3b, except for the neat KGM hydrogels that nearly remains The entrapment efficiencies (EEs) of 5-FU on KGM, KGM/SA-
constant. The swelling ratio of KGM/SA hydrogels increases with 1, KGM/SA-2, KGM/SA-3, KGM/SA/GO-1, KGM/SA/GO-2, and
increasing SA content. The swelling ratio of all KGM/SA hydrogels KGM/SA/GO-3, as determined by their UV spectra at 265 nm, are
obviously increases with increasing time (first stage), and then 10.29%, 13.32%, 15.50%, 17.49%, 22.73%, 27.09%, and 32.04%, respec-
decreases with further prolonging swelling time (second stage). tively. The results indicate that the more the GO content in the
The increase in the swelling ratio during the first stage is attributed hydrogels, the more is the 5-FU loading. This shows that the GO is
to the migration of water into the polymer network driven by indeed a promising candidate for drug carrier materials.
the osmotic pressure [31]. The decrease in the swelling ratio in
the second stage is attributed to the expansion of the SA poly- 3.4. 5-FU release behaviors
mer chains and the breakdown of the COO. . . Ca. . . OOC crosslinks
by PO4 3− anion in the media [27]. The partial dissolution of drug The controlled release behaviors of 5-FU from KGM, KGM/SA-
delivery vehicles is the main reason for the burst release of drugs, 3, and KGM/SA/GO-3 hydrogels at pH 1.2 HBS and pH 6.8 PBS are
which could be reduced by decreasing the dissolution rate and shown in Fig. 4a and b, respectively. The neat KGM and KGM/SA-
avoiding the disintegration of the vehicles. However, the swelling 3 hydrogels were found to release 98.77% and 86.00% of the
ratio of KGM/SA/GO hydrogels increases with increasing time. All entrapped 5-FU during 2 h in pH 1.2 HBS, respectively, whereas
KGM/SA/GO hydrogels maintain their original shape. This behav- only 32.55% of 5-FU was released from KGM/SA/GO-3 hydrogel
ior may be attributed to the physical crosslinking of GO with SA during this time and reached the equilibrium after 6 h (38.02%).
and KGM macromolecules, that overcomes the disintegration of the These results show that the prepared KGM/SA/GO-3 hydrogel could
gels. Further, the swelling ratio of KGM/SA/GO hydrogels decreases obviously inhibit the release of 5-FU from the hydrogel at low pH.
with increasing GO content because the interactions between the This behavior may reduce the gastric toxic effects. At pH 6.8 PBS, the
polysaccharides and GO strengthen as the content of GO increases. neat KGM and KGM/SA-3 hydrogels release 95.49% and 100% of the
Thus, the results indicate that KGM/SA/GO hydrogels can prevent entrapped 5-FU during 2 h, however, only 45.93% of the entrapped
the burst release of drugs. 5-FU was released from KGM/SA/GO-3 hydrogel during this time
228 J. Wang et al. / Colloids and Surfaces B: Biointerfaces 113 (2014) 223–229
Fig. 4. The controlled release behavior of 5-FU from KGM, KGM/SA-3, and
Fig. 3. The swelling kinetics of different hydrogels at pH 1.2 (a) HBS and 6.8 (b) PBS KGM/SA/GO-3 hydrogels at pH 1.2 (a) HBS and pH 6.8 (b) PBS at 37 ± 0.5 ◦ C. Each
at 37 ± 0.5 ◦ C. Each data point represents the mean ± S.D. of three determinations. data point represents the mean ± S.D. of three determinations.
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