Synthesis of photoresponsive hybrid alginate hydrogel with photo-controlled release behavior

Article abstract of DOI:10.1016/j.carbpol.2014.11.043

A photoresponsive hybrid alginate hydrogel was successfully prepared by Ca²⁺-mediated crosslinking reaction with a mixture of β-cyclodextrin-grafted alginate (β-CD-Alg) and diazobenzene-modified poly(ethylene glycol) (Az₂-PEG). The w

Full text of DOI:10.1016/j.carbpol.2014.11.043

Carbohydrate Polymers 119 (2015) 18–25
Contents lists available at ScienceDirect
Carbohydrate Polymers
journal homepage: www.elsevier.com/locate/carbpol
Synthesis of photoresponsive hybrid alginate hydrogel with
photo-controlled release behavior
a
a,b,∗
Chien-Ying Chiang , Chih-Chien Chu
a
School of Medical Applied Chemistry, Chung Shan Medical University, Taichung 40201, Taiwan
Department of Medical Education, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
b
a r t i c l e i n f o
a b s t r a c t
A photoresponsive hybrid alginate hydrogel was successfully prepared by Ca2+-mediated crosslink-
ing reaction with a mixture of ␤-cyclodextrin-grafted alginate (␤-CD-Alg) and diazobenzene-modified
poly(ethylene glycol) (Az2-PEG). The water-soluble Az2-PEG exhibits efficient trans-to-cis isomerization
of the terminal azobenzene moieties under UV-light irradiation and readily switched back to the initial
trans state under visible light. Because of low affinity between ␤-CD and cis-Az, the host–guest inclu-
sion complex formed by ␤-CD and trans-Az gradually dissociates under UV-light exposure. Accordingly,
the bulk gel exhibits substantial photo-induced transformation in gel morphology by the appearance of
significant comb-like cavities. This photosensitive behavior accompanied by the structural degradation
enables the rapid release of entrapped dye molecules under UV light stimulus. Moreover, an incident
light with higher power and mild acidic environment are capable of accelerating the photo-triggered
release, thus allowing the potential applications toward acute wound healing.
Article history:
Received 18 October 2014
Received in revised form
1
4 November 2014
Accepted 21 November 2014
Available online 28 November 2014
Keywords:
Alginate
Hydrogel
Azobenzene
Photoisomerization
Wound dressing
© 2014 Elsevier Ltd. All rights reserved.
1
. Introduction
Alginate, which is commonly isolated from brown algae, is
accommodate drugs and gradually release the drugs during the pro-
cess of gel swelling to prevent wound infection (August, Kong, &
Mooney, 2006; Bencherif et al., 2012; Pereira et al., 2013). How-
ever, alginates especially rich in GG blocks can incorporate more
ionic interactions between chains and usually form a gel with
high mechanical integrity. Therefore, during the controlled release
of drugs, a bulk alginate hydrogel is less responsive to exter-
nal stimuli such as temperature, pH level, and mechanical force.
Recently, Han et al. (2012) presented a pH-sensitive shape-memory
alginate hydrogel prepared by crosslinking a ␤-cyclodextrin (␤-
CD)-modified alginate and a diethylenetriamine-modified alginate.
Ariga and co-workers reported a controlled release system con-
taining a ␤-CD-crosslinked alginate gel triggered by a mechanical
stimulus (Izawa et al., 2013). The release of drugs from this gel sys-
tem was enhanced through mild mechanical compression because
of a change in the host–guest inclusion ability of CD moieties for
accommodating drug molecules.
Semiinterpenetrating networks (semi-IPNs) that are composed
of one crosslinked polymer system in which free polymer chains
are dissolved are capable of modulating the bulk properties
of gel networks (Matricardi, Pontoriero, Coviello, Casadei, &
Alhaique, 2008; Pescosolido et al., 2011). In semi-IPN systems,
both crosslinked and free polymers synergistically contribute to
the physicochemical properties of hybrid gels. Based on this con-
cept, we developed a photoresponsive hybrid alginate semi-IPN
that contains crosslinked ␤-CD-grafted alginate (␤-CD-Alg) and
an anionic linear polysaccharide composed of two saccharides:
epimeric ␤-d-mannuronate (M) and ␣-l-guluronate (G). The M and
G monomers are covalently bonded through 1,4-glycosidic linkages
and arranged into either homopolymeric blocks (MM and GG) or
alternating blocks (MGMG) along the polymeric backbone (Martins,
Sarmento, Souto, & Ferreira, 2007; Gattás-Asfura & Stabler, 2009;
García-González, Alnaief, & Smirnova, 2011; Gong et al., 2011;
Goh, Heng, & Chan, 2012). According to the “egg-box” model, two
facing GG blocks can be coordinated with divalent ca ions, result-
ing in interchain crosslinking and hydrogel formation (Sikorski,
Mo, Skjåk-Bræk, & Stokke, 2007; Coleman et al., 2011; Narayanan,
Melman, Letourneau, Mendelson, & Melman, 2012; Cui et al., 2013).
Alginate hydrogels have high water content, elasticity, and
the ability to maintain a physiologically moist microenvironment
in the wound bed; therefore, they are widely applied in tissue
engineering (Patterson, Martino, & Hubbell, 2010; Sun & Tan,
2+
2
013; Bozza et al., 2014). Moreover, alginate wound dressings can
∗ Corresponding author at: School of Medical Applied Chemistry, Chung Shan
Medical University, No. 110, Sec. 1, Jianguo N. Rd., Taichung 40201, Taiwan.
Tel.: +886 4 2324 8189; fax: +886 4 2324 8189.
E-mail addresses: jrchu@csmu.edu.tw, jrchu3933@gmail.com (C.-C. Chu).
http://dx.doi.org/10.1016/j.carbpol.2014.11.043
0
144-8617/© 2014 Elsevier Ltd. All rights reserved.

C.-Y. Chiang, C.-C. Chu / Carbohydrate Polymers 119 (2015) 18–25
19
Scheme 1. Preparation protocol of a photoresponsive hybrid alginate hydrogel that contains crosslinked ␤-CD-grafted alginate (␤-CD-Alg) and interpenetrating
diazobenzene-terminated poly(ethylene glycol) (Az2-PEG). Red-colored rhodamine B (RhB) is the mimic of entrapping drug molecules.
interpenetrating diazobenzene-terminated poly(ethylene glycol)
Az -PEG), as shown in Scheme 1. Because of the size and shape
an Ostwald–Fenske viscometer using distilled water as a stan-
dard.
(
2
of the CD cavity, trans-Az and ␤-CD can form a favorable inclusion
complex through host–guest affinity, whereas cis-Az is excluded
from the complexation (Yuen & Tam, 2010; Tan et al., 2012). There-
fore, the hybrid gel network features Ca2+ ions as cross-linkers as
well as numerous junction points composed of ␤-CD and trans-
Az inclusion complexes. Moreover, UV light irradiation induces
efficient trans-to-cis isomerization (Peng, Tomatsu, & Kros, 2010;
Tamesue, Takashima, Yamaguchi, Shinkai, & Harada, 2010; Meng
et al., 2011). Accordingly, the hybrid alginate hydrogel is sensitive
to the UV light used to facilitate trans-to-cis photoisomerization,
which results in the dissociation of the inclusion complex and par-
tial gel degradation. Thus, a light trigger can accelerate the release
rate of small molecules entrapped within the gel. In addition to
causing spontaneous drug release during gel swelling, this strategy
entails using a bulk alginate hydrogel as a photocontrollable release
system.
The hydrogel samples containing rhodamine B (RhB) with a
strong fluorescence at ꢁmax = 580 nm were irradiated with 365 nm
LED, and the reflective emission from the samples were collected
and induced by a fiber bundle into a CCD imaging spectrometer
(USB-4000, Ocean Optics) for the spectra recording. To carry out
trans-to-cis photoisomerization, the samples were also excited by
365 nm LED for a specific time interval and in situ analyzed by the
same experimental apparatus (see Fig. S1 in Supporting informa-
tion).
2
2
.2. Materials synthesis and characterization
.2.1. Synthesis of (E)-4-(p-tolyldiazenyl)phenol (1)
An aqueous solution of NaNO2 (1.91 g, 27.7 mmol) was slowly
added into a solution of p-toluidine (1.52 g, 14.2 mmol) in 30 mL of
◦
3
M HCl, and then the mixture was stirred under 0 C for 30 min,
followed by adding an aqueous buffer solution containing phenol
2
. Experimental
(
1
1.71 g, 18.2 mmol), NaOH (0.73 g, 18.2 mmol), and Na CO (1.93 g,
2 3
◦
8.2 mmol). After stirred at 0 C for 30 min, the mixing solution
2.1. General methods
was extracted by ethyl acetate for 3 times. The combined organic
phase was dried over anhydrous magnesium sulfate, and rotary
evaporation to dryness afforded the crude product. Further purifi-
All reactions were carried out under a nitrogen atmosphere.
All solvents were dried following standard procedures. Sodium
cation was performed on flash column chromatography (SiO , ethyl
2
5
alginate (Mw = 1.2–1.4 × 10 Da) and poly(ethylene glycol) diglycidyl
acetate/hexane = 2:8, R = 0.4) to yield the final product 1 as orange
f
3
ether (Mn = 2 × 10 Da) were purchased from Sigma-Aldrich, and
solid (2.41 g, 80%). 1H NMR (400 MHz, CDCl ): ı = 7.84 (d, J = 8.8 Hz,
3
other chemical reagents were obtained as high-purity reagent-grade
from commercial suppliers and used without further purification.
Flash column chromatography was performed on spherical sil-
2
2
H), 7.78 (d, J = 8.3 Hz, 2H), 7.29 (d, J = 8.3 Hz, 2H), 6.91 (d, J = 8.8 Hz,
H), 5.74 (bs, 1H), 2.42 (s, 3H).
1
ica gel with 75-200 um particle dimensions. H (400 MHz) and
13
2.2.2. Synthesis of
C (100 MHz) NMR spectra were recorded on a Varian Mer-
(
E)-1-(4-(2-bromoethoxy)phenyl)-2-(p-tolyl)diazene (2)
To a anhydrous THF solution of 1 (1.5 g, 7.1 mmol), K CO (6.8 g,
cury Plus 400 MHz spectrometer at room temperature. Spectral
processing (Fourier transform, peak assignment and integration)
was performed using MestReNova 6.2.1 software. Trans/cis photo-
isomerization for the azobenzene-containing polymers dissolved
in organic solvents was carried out under the exposure of light-
emitting diodes (LEDs) at 365 and 470 nm and an output power
of 10 W. Ultraviolet–visible (UV–vis) absorption spectra were per-
formed on a Thermo Genesys 10S UV–vis spectrometer equipped
with a thermostatic cuvette holder. Field emission scanning elec-
tron microscopy (FE-SEM) was performed on a Jeol JSM-6700F
instrument equipped with a cold-cathode field emission gun. The
UV–vis measurement was carried out under a constant tempera-
ture. The relative viscosity (ꢀr) measurement was performed on
2
3
4
9 mmol), and 18-crown-6 (20 g, 75 mmol), 1,2-dibromoethane
(
27 g, 0.14 mol) was added dropwisely over 30 min under N atmo-
2
◦
sphere. The mixture was stirred at 45 C for overnight and then
extracted by ethyl acetate for 3 times. The combined organic
phase was dried over anhydrous magnesium sulfate, and rotary
evaporation to dryness afforded the crude product. Further purifi-
cation was performed on flash column chromatography (SiO , ethyl
2
acetate/hexane = 2:8, R = 0.6) to yield the final product 2 as orange
f
solid (1.9 g, 84%). 1H NMR (400 MHz, CDCl ): ı = 7.90 (d, J = 9.1 Hz,
3
2
2
H), 7.79 (d, J = 8.3 Hz, 2H), 7.30 (d, J = 8.3 Hz, 2H), 7.01 (d, J = 9.1 Hz,
H), 4.36 (t, J = 6.3 Hz, 2H), 3.67 (t, J = 6.3 Hz, 2H), 2.43 (s, 3H).

2
0
C.-Y. Chiang, C.-C. Chu / Carbohydrate Polymers 119 (2015) 18–25
(a)
(b)
(c)
4000
3500
3000
2500
2000
1500
-1
Wavenumber(cm )
(d)
1650
1565
1606
1728
Fig. 2. (a) The absorbance change in ␲–␲* and n–␲* transitions of Az2-PEG solu-
tion upon 365-nm LED excitation. (b) Reversible change in ␲–␲* absorbance by
alternating 365-nm and 470-nm light irradiation.
1800
1750
1700
1650
1600
1550
1500
2H), 4.06 (t, J = 5.1 Hz, 2H), 3.12 (t, J = 5.1 Hz, 2H), 2.42 (s, 3H) 1.39
(bs, 2H).
-1
Wavenumber (cm )
2.2.5. Synthesis of diazobenzene-terminated poly(ethylene
Fig. 1. FT-IR spectra of (a) sodium alginate, (b) mono-6-amino-␤-CD, and (c) ␤-CD-
Alg. (d) Peak deconvolution in the selected region shows the characteristic amide
stretching at 1650 and 1565 cm , and carboxylate stretching at 1606 cm .
glycol) (Az2-PEG)
−
1
−1
An anhydrous DMF solution of Az (0.13 g, 0.51 mmol) and
poly(ethylene glycol) diglycidyl ether (0.5 g, 0.25 mmol) was stirred
◦
2
(
.2.3. Synthesis of
E)-1-(4-(2-azidoethoxy)phenyl)-2-(p-tolyl)diazene (3)
An anhydrous DMF solution of 2 (1.5 g, 4.7 mmol) and NaN
at 100 C under N2 atmosphere until the complete disappearance of
Az. The DMF was removed under vacuum, and then the mixture was
extracted by ethyl acetate for 3 times. The combined organic phase
was dried over anhydrous magnesium sulfate, and rotary evapo-
ration to dryness afforded the crude product. Further purification
was performed on flash column chromatography (SiO2, methanol,
Rf = 0.6) to yield the final product Az2-PEG as dark-yellow solid
(0.4 g, 80%).
3
◦
3.2 g, 49 mmol) was stirred at 100 C for overnight under N atmo-
2
(
sphere. The DMF was removed under vacuum, and then the mixture
was extracted by ethyl acetate for 3 times. The combined organic
phase was dried over anhydrous magnesium sulfate, and rotary
evaporation to dryness afforded the final product 3 (1.1 g, 83%). 1
H
NMR (400 MHz, CDCl ): ı = 7.91 (d, J = 9.1 Hz, 2H), 7.79 (d, J = 8.3 Hz,
3
2
2
H), 7.30 (d, J = 8.3 Hz, 2H), 7.02 (d, J = 9.1 Hz, 2H), 4.22 (t, J = 6.3 Hz,
H), 3.64 (t, J = 6.3 Hz, 2H), 2.43 (s, 3H).
2.2.6. Synthesis of ˇ-cyclodextrin-grafted alginate (ˇ-CD-Alg)
The mono-6-amino-␤-CD was synthesized following the pub-
lished procedure (Lin, Tsai, Tu, Jeng, & Chu, 2013). An aqueous buffer
solution containing sodium alginate (108 mg, 2.4 mmol of COOH)
and N-hydroxysuccinimide (1.61 g, 13.9 mmol) was slowly added
by another aqueous solution of 1-(3-dimethylaminopropyl)-3-
ethylcarbodiimide hydrochloride (2.67 g, 13.9 mmol). The reaction
2.2.4. Synthesis of
(
E)-2-(4-(p-tolyldiazenyl)phenoxy)ethanamine (Az)
An anhydrous DMF solution of 3 (1.5 g, 5.3 mmol) and PPh3
6.3 g, 24 mmol) was stirred at room temperature for 2 h under N2
(
◦
atmosphere, followed by adding 5.3 mL of water and then stirred
at 90 C for another 3 h. The DMF was removed under vacuum, and
then the mixture was extracted by ethyl acetate for 3 times. The
combined organic phase was dried over anhydrous magnesium sul-
fate, and rotary evaporation to dryness afforded the crude product.
Further purification was performed on flash column chromatogra-
mixture was stirred at 4 C for 10 min, followed by adding
◦
an aqueous solution of mono-6-amino-␤-CD (2.82 g, 2.4 mmol).
After reacting for another 12 h, the mixture was purified by
membrane dialysis (molecular weight cut-off = 12,000–14,000 Da)
against water for 3 days until complete removal of all the reagents,
and lypophilization yields the final product as white powder. The
1
phy (SiO , methanol, R = 0.3) to yield the final product Az as orange
solid (1.1 g, 81%). H NMR (400 MHz, CDCl ): ı = 7.90 (d, J = 9.0 Hz,
H NMR spectra are shown in Fig. S1. Based on the integral peak
2
f
1
area (S1) of characteristic H-1 proton of ␤-CD (ı = 5.1 ppm) and the
integral peak area (S2) of alginate protons from ı = 3.5–4.0 ppm,
3
2
H), 7.79 (d, J = 8.5 Hz, 2H), 7.29 (d, J = 8.5 Hz, 2H), 7.01 (d, J = 9.0 Hz,

C.-Y. Chiang, C.-C. Chu / Carbohydrate Polymers 119 (2015) 18–25
21
Scheme 2. Synthetic route of diazobenzene-terminated poly(ethylene glycol) (Az2-PEG).
II: 1565 cm 1) joined the alginate and ␤-CD, and free carboxylate
−
degree of substitution (DS) of ␤-CD along the polymer was deter-
mined following the relationship of DS = (S1/7)/[(S2-4S1)/4] (Han
et al., 2012).
−
1
stretching was 1606 cm (Fig. 1).
The relative viscosity (ꢀr) measurement for 1 wt% aqueous solu-
tions of pristine alginate and ␤-CD-Alg indicated that the ꢀr values
of the polymer solutions decreased as the ␤-CD feeding ratios
increased (Fig. S3). This result confirmed that ␤-CD-Alg with var-
ious ␤-CD grafting ratios was synthesized and that the dangling
2.2.7. Preparation of hybrid alginate hydrogel
An aqueous solution containing ␤-CD-Alg (15 mg), Az -PEG
2
−2
(
7 mg), and RhB (10 M, 0.5 mL) was blended thoroughly by vortex
␤
-CD moieties along the alginate backbone effectively reduced the
mixer, and the hydrogel was immediately formed as the mixture
was added into 10% of CaCl2 solution through a syringe. The bulk
hydrogel was repeatedly rinsed with water until free red-colored
dye molecules was completely removed from the gel network.
viscosity of the polymer solution. In preparing an alginate hydro-
gel, the viscosity of the alginate solution is critical, and therefore the
degree of ␤-CD substitution was optimized. In addition, because the
alginate crosslinking was mainly attributed to the coordination of
2+
Ca ions with the carboxylate groups of two facing GG blocks, non-
selective ␤-CD functionalization onto either M or G units exerted a
substantial influence on the crosslinking property of the hydrogel.
We discovered that higher ␤-CD grafting ratios along the back-
bone prohibited the crosslinking of each polymer chain and, thus,
formed hydrogels may lose their mechanical integrity. Therefore,
for preparing a crosslinkable hydrogel with a suitable mechanical
strength, the feeding molar ratio of ␤-CD to the carboxylate groups
were determined to be 1, and the average degree of substitution
was approximately 0.17 according to NMR analysis.
The Az2-PEG, which acted as the second component in the
semi-IPN gel system, was simply prepared through a substitution
reaction of diepoxy PEG with amine-modified Az (Scheme 2). The
photoisomerization of the Az molecules at PEG chain ends was
analyzed using UV–vis absorption spectra. As shown in Fig. 2a,
the decrease in ␲–␲* absorbance from 2.6 to 1.2 at ꢁmax = 340 nm
clearly confirmed that trans-to-cis isomerization occurred upon
UV light irradiation, and alternating UV and visible light
3
. Results and discussion
Alginate polymers with varying degrees of ␤-CD substitution
were first synthesized through carbodiimide-promoted amida-
tion by using a commercially available sodium alginate and
mono-6-amino-␤-CD in various feeding ratios with respect to
the carboxylate groups in an 2-(N-morpholino)ethanesulfonic acid
(
MES) buffer (pH = 5.8) (Yang, Xie, & He, 2011). The resulting
polymers were purified through dialysis to remove unreacted ␤-
CD derivatives and then characterized using H NMR and FT-IR
analysis. Although the proton resonance exhibited by the polysac-
charides on the ␤-CD ring and the alginate backbone substantially
overlapped in the range of ␦ = 3.5 − 4.0 ppm, the appearances of the
characteristic anomeric protons at ı = 5.1 ppm clearly indicated that
1
␤
-CD was functionalized onto the alginate (Fig. S2) (Han et al., 2012;
Izawa et al., 2013; Lin et al., 2013). Moreover, IR peak deconvolution
in the selected region, confirming that an amide bond (I: 1650 and

2
2
C.-Y. Chiang, C.-C. Chu / Carbohydrate Polymers 119 (2015) 18–25
Fig. 3. The change in transmittance at ꢁ = 630 nm for an aqueous mixture containing
Az2-PEG and ˇ-CD. The image shows a transparent solution (a) becomes opaque (b),
indicating the formation of host–guest inclusion complex of these two components.
exposure resulted in a rapid, reversible photoswitch between the
trans and cis states (Fig. 2b). Moreover, the host–guest reaction
between Az -PEG and ␤-CD was characterized according to the tur-
2
bidity of the complex solution by using an incident beam at 630 nm
(
Ikeda, Ooya, & Yui, 1999). As shown in Fig. 3, the initial transparent
solution became turbid after the two components were mixed for
h, and the transmittance decreased to approximately 65%. This
1
result confirmed that inclusion complexes formed.
The hybrid alginate hydrogel was prepared through the drop-
wise addition of the ␤-CD-Alg (15 mg/mL) and Az -PEG (7 mg/mL)
2
mixtures into an aqueous CaCl2 solution. To mimic the release
of small drug molecules, red-colored rhodamine B (RhB) with a
strong fluorescence at ꢁmax = 580 nm was incorporated into the
hybrid gel. Fig. 4a shows images and fluorescence spectra of an
RhB-containing hydrogel stored in the dark. A slight decrease in
fluorescence intensity within 60 min indicated the spontaneous
release of RhB molecules into the surrounding water during gel
swelling. Studies have reported that alginate hydrogels release
hydrophobic curcumin molecules over a period of up to 20 days
(Dai et al., 2009). By contrast, in the current study, the hybrid gel
exhibited a substantial decrease in fluorescence intensity after 365-
nm LED light irradiation, and it was almost colorless after UV light
exposure for 60 min, as shown in Fig. 4b. Moreover, we examined
the light-triggered release of a control hydrogel that contained only
␤
-CD-Alg and RhB. Fig. 4c shows the results of a quantitative anal-
ysis of the change in fluorescence intensity of the control gel and
hybrid gel systems upon light exposure. Only a slight decrease in
the fluorescence intensity of the control gel precluded the photo-
bleaching effect of RhB dyes produced through UV light irradiation
and thus confirmed that the phototriggered rapid release of RhB
molecules from the hybrid gel was successful. According to our
thorough review of relevant research, this is the first report of
the photocontrolled release of a bulk alginate hydrogel through a
photoresponsive Az and ␤-CD inclusion complex.
Fig. 4. Fluorescence spectra (ꢁex = 365 nm) and images of an RhB-containing hybrid
hydrogel (a) stored in the dark and (b) upon UV-light exposure. (c) Quantitative
analysis of the change in fluorescence intensity of the control gel (᭹) and hybrid gel
(
ꢀ). The control gel contains only ␤-CD-Alg and RhB.
compared hybrid hydrogels with contents of Az -PEG ranging from
2
0.04 to 7 mg/mL. As shown in Fig. 5b, the release rate increased as
the content of photoresponsive moieties increased, clearly suggest-
We speculated that UV-light-induced trans-to-cis photoiso-
merization results in the dissociation of the host–guest complex of
ing that greater Az -PEG contents engendered faster drug release
2
␤
-CD and cis-Az, thus agitating the IPN framework of the hybrid
upon UV light irradiation.
gel system. Consequently, the RhB molecules could be released
from the bulk hydrogel more quickly upon UV light irradiation. As
shown in Fig. 5a, our assumption was supported by two controlled
experiments: (1) The release rate was increased by increasing the
power of a UV lamp because more efficient photoisomerization
yields more cis isomers; and (2) 470-nm LED light irradiation did
not induce accelerated RhB release because trans-to-cis isomeriza-
tion can be conducted only at a specific wavelength. In addition, we
The change in the morphology of the photoresponsive hybrid
hydrogels upon light stimulus was analyzed using scanning elec-
tron microscopy. Fig. 6a shows the ␤-CD-Alg hydrogel before and
after UV light irradiation. The surface morphology was almost
unchanged under light exposure, suggesting that the controlled
hydrogel was insensitive to the UV light. This result confirmed
that the accumulative heat during LED light exposure exerted
no influence on the gel structure. Compared with a pristine Alg

C.-Y. Chiang, C.-C. Chu / Carbohydrate Polymers 119 (2015) 18–25
23
Fig. 5. (a) The change in fluorescence intensity of the hybrid hydrogels exposed
to 365-nm light with lower (10 W) and higher (100 W) output energy and to 470-
nm LED (10 W). (b) The change in fluorescence intensity of the hybrid hydrogels
composed of an increasing amount of Az2-PEG.
Fig. 7. (a) A pH-dependency of RhB releasing from hybrid hydrogel upon UV-light
irradiation. (b) A stepped RhB releasing by alternating phototriggered and sponta-
neous processes. The hydrogel was irradiated with UV light at 0, 10, 20 min and
exposed to darkness at 5, 15, 25 min.
Fig. 6. Scanning electron microscopy (SEM) images of (a) ␤-CD-Alg hydrogel and (b) hybrid hydrogel before and after UV-light irradiation.

2
4
C.-Y. Chiang, C.-C. Chu / Carbohydrate Polymers 119 (2015) 18–25
hydrogel exhibiting a smoother surface (Fig. S4), the structural
integrity of the ␤-CD-Alg hydrogel with cracks on the surface was
slightly lower. The loss of structural integrity may moderately
enhance the release of RhB from the ␤-CD-modified hydrogel; this
speculation is consistent with the fluorescence profile shown in
Appendix A. Supplementary data
Supplementary data associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/j.carbpol.
2014.11.043.
Fig. 4c. Regarding the hybrid hydrogel system composed of Az -PEG
2
and ␤-CD-Alg, Fig. 6b shows a substantial change in morphology
upon UV light irradiation. The formation of comb-like cavities on
the surface clearly indicated phototriggered structural degrada-
tion, which is mainly due to the photosensitive properties of the
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-CD and Az inclusion complexes. Because of efficient trans-to-
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In conclusion, we demonstrated a smart hybrid alginate hydro-
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through UV light irradiation. The hybrid gel was prepared based
on a semi-IPN structure composed of a crosslinked ␤-CD-grafted
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2
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2+
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the cis-Az from ␤-CD. Moreover, this photosensitive behavior was
accompanied by substantial structural degradation of the hybrid
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neering, in vitro and in vivo biological study of the applications of
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The authors would like to thank the Ministry of Science and
Technology of Taiwan (MOST102-2113-M-040-004) for financially
supporting this research.

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