Synthesis and characterization of in situ photogelable polysaccharide derivative for drug delivery

Article abstract of DOI:10.1016/j.ijpharm.2010.04.011

A novel polysaccharide derivative with photoreactivity was prepared by the conjugation of carboxymethylated chitosan with N-hydroxyl succinimide-activated nitrocinnamate in the presence of N,N-dicyclohexylcarbodiimide, and characterized by IR, ¹

Full text of DOI:10.1016/j.ijpharm.2010.04.011

International Journal of Pharmaceutics 393 (2010) 96–103
Contents lists available at ScienceDirect
International Journal of Pharmaceutics
journal homepage: www.elsevier.com/locate/ijpharm
Synthesis and characterization of in situ photogelable polysaccharide derivative
for drug delivery
Rong Hu, Yu-Yun Chen, Li-Ming Zhang∗
Key Laboratory for Designed Synthesis and Application of Polymer Materials, School of Chemistry and Chemical Engineering, and Key Laboratory for Polymeric Composite and
Functional Materials of Ministry of Education, Sun Yat-Sen (Zhongshan) University, No. 135, Xingangxi Road, Guangzhou 510275, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel polysaccharide derivative with photoreactivity was prepared by the conjugation of car-
boxymethylated chitosan with N-hydroxyl succinimide-activated nitrocinnamate in the presence of
N,N-dicyclohexylcarbodiimide, and characterized by IR, 1H NMR, UV–vis and rheological analyses. It
was found that such a modified polysaccharide could exhibit an unique photogelation ability in the
absence of potentially toxic photoinitiator or catalyst and be suitable particularly for the in situ prepara-
tion of photocrosslinked hydrogel biomaterials. By changing the photoirradiation time and incorporated
nitrocinnamate content, its photogelation property could be modulated. For the resultant hydrogels
incorporated with various nitrocinnamate contents, their properties such as swelling, viscoelasticity,
in vitro biodegradation and drug release were investigated. In addition, the photogelation mechanism of
this polysaccharide derivative was also discussed.
Received 17 November 2009
Received in revised form 19 March 2010
Accepted 12 April 2010
Available online 24 April 2010
Keywords:
Polysaccharide derivative
Photoreactivity
Photogelation ability
Photocrosslinked hydrogel
Drug release
© 2010 Elsevier B.V. All rights reserved.
1. Introduction
terial preparation in the field of medicinal and biomedical science.
In this context, a common strategy for photoinduced hydrogel for-
Naturally occurring polysaccharides are hydrophilic macro-
molecules suitable for the development of hydrogel biomaterials
(Liu and Chan-Park, 2009; Kopecˇek, 2007; Hennink and van
Nostrum, 2002; Zhang et al., 2005a,b; Liang et al., 2007; Zhao
et al., 2006). They possess a number of favorable characteristics
such as high hydrophilicity, good biocompatibility, lack of toxi-
city, and availability of reactive sites for chemical modification.
Hydrogels derived from the crosslinking of polysaccharides and
their derivatives have been investigated in a number of biotechnical
and biomedical applications, ranging from controlled drug deliv-
ery systems and enzyme immobilization matrices to size-selective
biomembranes and wound healing dressings (Song et al., 2009;
Hoare and Kohane, 2008; Leach et al., 2003).
Among various methods used for the polysaccharide gela-
tion, photoinduced crosslinking provides an effective and benign
method of in situ hydrogelation. This is because that facile photo-
gelation exhibits considerable advantages when compared to the
conventional methods of physical or chemical hydrogel formation,
including mild reaction conditions, minimum byproduct forma-
tion, and easily controlled processing. Therefore, there has been an
increasing interest in utilizing photogelation as a means of bioma-
mation involves a polymerizable polysaccharide derivative having
pendant acrylate groups along the polysaccharide backbone chain,
which is usually obtained by the reaction of the polysaccharide with
maleic anhydride or glycidyl methacrylate (Li and Zhang, 2007;
Kim et al., 1999; Li et al., 2004; Smeds et al., 2001). In this method,
the photosensitive polysaccharide derivatives are polymerized in
the presence of a photoinitiator (such as benzophenone and xan-
thene dyes), and a catalyst or an accelerator, upon exposure to
long-wavelength ultraviolet radiation (UV) or visible light.
Chitosan is
a
copolymer of d-glucosamine and N-
acetylglucosamine derived from chitin (Mi et al., 2002). It
was reported that chitosan is a potentially useful pharmaceutical
material owing to its good biocompatibility and low toxicity
(Nakatsuka and Andrady, 1992; Thacharodi and Rao, 1993). For
drug delivery applications, chitosan needs to be crosslinked due
to its hydrophilic property. Various crosslinking agents such as
formaldehyde and glutaraldehyde have been used to prepare
chitosan hydrogels (Illum, 1998; Risbud et al., 2000). In this
work, we prepare and characterize a novel water-soluble chitosan
derivative with nitrocinnamate as pendant groups. Different
from the photocrosslinkable polysaccharide derivatives reported
previously in the literature, this modified polysaccharide has a
unique photogelation ability in the absence of potentially toxic
photoinitiator or catalyst, which makes it to be suitable particu-
larly for photoinduced formation of hydrogel biomaterials. It is
known (Lewis et al., 1988) that cinnamate can undergo trans–cis
∗
Corresponding author: Tel.: +86 20 84112354; fax: +86 20 84112354.
E-mail address: ceszhlm@mail.sysu.edu.cn (L.-M. Zhang).
0378-5173/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.ijpharm.2010.04.011

R. Hu et al. / International Journal of Pharmaceutics 393 (2010) 96–103
97
(Nexus 670, Nicolet Co., USA) and 1H NMR analyses were used to
confirm the conjugation reaction.
isomerization and [2 + 2] cycloaddition upon UV irradiation at
wavelengths longer than 290 nm. Such a photocrosslinking prop-
erty has been broadly utilized in the field of photolithography
and the semiconductor industry (Reiser, 1989). To our knowledge,
however, the application of nitrocinnamate photoreactivity in
the formation of polysaccharide-based hydrogels as well as the
resultant hydrogel properties have rarely been explored.
2.3. Photogelation of aqueous CMCS-NC solution and its
characterization
Photogelation for aqueous solution (5.0%) of CMCS-NC sample
(CMCS-NC-1 or CMC-NC-2, Wsolid) was performed on a Teflon dish
by photoirradiation, using a 200 W mercury UV lamp (365 nm) with
an intensity of 0.9 mW/cm2 (Philips UV lamp, Shanghai Yayuan
Lighting Appliance Co., China) for a predetermined time (20, 30, 40,
50 or 60 min). The gelled sample obtained was immersed in distilled
water at room temperature for 24 h to remove unreacted CMCS-NC
and then weighed (Wwet) after the careful removal of excess water.
The vacuum-dried hydrogel was weighed (Wdry). The gelation effi-
ciency (GE) was calculated using the following equation:
2. Materials and methods
2.1. Materials
Chitosan (75–85% deacetylated; brookfield vicosity, 20–200 cp
at 1% concentration in 1% acetic acid), lysozyme and N,N-
dicyclohexylcarbodiimide (DCC) were purchased from Sigma.
4-Nitrocinnamate acid (NC) was supplied by Aladdin-reagent Inc.
Doxorubicin hydrochloride was obtained from BioBasic Inc., USA.
N-Hydroxyl succinimide (NHS) was obtained from Sinopharm
Chemical Reagent Co., Ltd. All other chemicals were of analytical
grade and were obtained from Aldrich.
Wdry
GE(%) =
× 100
(1)
Wsolid
The swelling degree (SD) was calculated as follows:
Wwet − Wdry
SD =
(2)
2.2. Synthesis of water-soluble chitosan derivative (CMCS-NC)
containing nitrocinnamate moiety and its characterization
Wdry
For aqueous CMCS-NC solution before and after photoirradi-
ation, their rheological characterization was taken on an ARES
rheometer (TA Co., USA). The storage and loss moduli were mea-
sured as a function of frequency under oscillatory shear at a strain
of 0.5%, which was within the linear viscoelastic region. The UV/vis
spectra of aqueous CMCS-NC solution during photoirradiation were
investigated as a function of irradiation time (0–20 min). For the
resultant hydrogels, their morphologies were observed by using
a Hitachi S 4800 scanning electron microscope (Japan) with an
accelerating voltage of 5 kV. The hydrogel samples were allowed
to lyophilize and then coated with a thin layer of gold.
A three-step reaction strategy shown in Scheme 1 was used
to prepare water-soluble chitosan derivative (CMCS-NC) con-
taining nitrocinnamate moiety. For this purpose, water-soluble
carboxymethylated chitosan (CMCS) was firstly synthesized by the
reaction of chitosan (10 g) and chloroacetic acid (25 g) in isopropyl
alcohol/H2O (volume ratio, 2:1) mixed solvent (150 mL) accord-
ing to the procedure reported previously (Liang and Zhang, 2007),
and its carboxymethyl substitution degree was determined to be
0.72 by potentiometric titration method (Riccardo et al., 1982). To
obtain NHS-activated nitrocinnamate (NHS-NC), 4-nitrocinnamate
acid (1.93 g) was mixed with NHS (1.20 g) and DCC (2.10 g) in
N,Nꢀ-dimethylformamide (DMF, 35 mL) at 40 ◦C. The mixture was
reacted for 24 h at room temperature. The precipitated dicyclohexyl
urea was removed by filtration. The filtrate was precipitated by
water, and the precipitate was recrystallized in DMF and ethanol
to give yellowish NHS-NC powder (yield, 75.2%). The following
1H NMR data (DMSO-d6, ppm), which were obtained by a Varian
Mercury-Plus (300 MHz) spectrometer, confirmed the formation of
NHS-NC: 2.85 (s, 4H), 7.18 (d, 1H), 7.23 (d, 1H), 8.12 (d, 2H) and 8.26
(d, 2H).
For the conjugation of CMCS with NHS-NC, CMCS (0.4 g) was
dissolved in aqueous sodium bicarbonate solution (50 mL, pH 8.3),
and the resultant solution was diluted with DMF (40 mL) under stir-
ring. After that, a DMF solution (10 mL) of NHS-NC (0.240 or 0.150 g)
was added dropwise. The reaction was carried out for 72 h at room
temperature in the dark. Upon reaction completion, the reaction
mixture was poured into THF (150 mL). The resultant precipitate
was separated from the solution by filtration. Reprecipitation was
carried out several times in water–THF system until there was no
free NHS-NC in the filtrate, which was detected by UV analysis. After
the last precipitate was dried at 40 ◦C under vacuum, CMCS-NC was
obtained. By changing the amount of NHS-NC, two CMCS-NC sam-
ples with various NC contents were prepared, namely CMCS-NC-1
(yield, 65.5%) for the sample obtained when 0.240 g NHS-NC was
used, and CMCS-NC-2 (yield, 71.2%) for the sample obtained when
0.150 g NHS-NC was used. The degree of substitution (DS) of the
introduced nitrocinnamate groups was expressed as the number of
incorporated nitrocinnamate groups per 100 anhydroglucose units
of CMCS, and was determined by the UV–vis spectra (TU-1901, Bei-
jing Purkinje Co., China). As a result, the DS value was found to
be 11.2 for CMCS-NC-1, and 1.9 for CMCS-NC-2, respectively. FTIR
2.4. In vitro degradation of CMCS-NC hydrogels
In vitro degradation of CMCS-NC hydrogels was investigated
according to the method reported by Amsden et al. (2007). For this
purpose, the dried CMCS-NC hydrogels were incubated in a mix-
ture of 4 mg/mL lysozyme from chicken egg white and 0.1% (w/v)
sodium azide with a gentle shaking at 37 ◦C. The lysozyme mixture
solution was changed every 10 days. Every 10 days, the hydrogel
samples were taken out from the lysozyme solution, rinsed with
deionized water, dried for 48 h and weighed to obtain the final
weight after degradation. The extent of in vitro degradation was
expressed as the percentage of the weight loss of the dried hydrogel
after lysozyme treatment.
2.5. Drug loading by CMCS-NC hydrogel and in vitro release
For the in situ loading of doxorubicin (DOX) as the model drug,
a known amount of doxorubicin was added to aqueous CMCS-NC
solution according to the DOX/CMCS-NC mass ratio of 20 mg/g, and
was mixed manually until homogeneous. After that, UV irradia-
tion (365 nm) was conducted for 45 min to induce the gelation of
mixed CMCS-NC/DOX solution. The formed hydrogel was soaked
in 10 mL PBS solution pre-heated to 37 ◦C and incubated in water
bath at 37 ◦C under mild shaking motion (50 rpm). PBS solutions
were periodically renewed with fresh buffer. The amount of DOX
released into the buffer was determined using UV–vis spectroscopy
at a wave length of 481 nm and the total amount released was calcu-
lated from the established standard curve. All release studies were
carried out in triplicate.

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R. Hu et al. / International Journal of Pharmaceutics 393 (2010) 96–103
Scheme 1. A three-step reaction strategy for the preparation of water-soluble chitosan derivative (CMCS-NC) containing nitrocinnamate moiety.
3. Results and discussion
The water-soluble chitosan derivative (CMCS-NC) with pho-
toreactivity was prepared in this study by the conjugation of
carboxymethylated chitosan (CMCS) with NHS-activated nitrocin-
namate (NHS-NC) in the presence of DCC, as illustrated in Scheme 1.
To confirm the conjugation reaction, FTIR and 1H NMR analyses
were carried out for purified CMCS and it’s conjugate (CMCS-NC-1).
From the FTIR spectra shown in Fig. 1, it was found that the spec-
trum of the conjugate showed not only the characteristic stretching
vibrations of CMCS at 3427 cm−1 (O–H stretch overlapped with
N–H stretch), 2924 cm−1 (C–H stretch), 1602 and 1415 cm−1 (C=O
stretch), 1325 cm−1 (C–N stretch) and 1070 cm−1 (C–O stretch)
(Wang et al., 2007), but also the additional shoulder peaks at
1500 and 1400 cm−1, which could be assigned to the characteristic
absorptions of benzene ring in the incorporated NC groups. More-
over, the absorption peak of the conjugate at 1662 cm−1 become
stronger, which could be attributed to the carbonyl stretch of sec-
ondary amides (amide I band). From the 1H NMR spectra shown
in Fig. 2, it was found that the spectrum of the conjugate showed
not only the characteristic proton peaks of CMCS at 1.95 ppm (CH3,
acetyl group of of N-acetamidoglucose units), 2.60 ppm (CH, carbon
2 of N-unsubstituted glucosamine units), 3.1–4.0 ppm (CH, carbon
3, 4, 5 and 6 of glucosamine units) and 4.35 ppm (–CH2COOH, car-
Fig. 1. IR spectra of CMCS and its conjugate (CMCS-NC-1) sample (KBr pellets).

R. Hu et al. / International Journal of Pharmaceutics 393 (2010) 96–103
99
Fig. 4. The swelling degree as a function of irradiation time for the hydrogels formed
from 5.0% aqueous solutions of CMCS-NC samples upon exposure to 365 nm radia-
tion in the absence of photoinitiator.
Fig. 2. 1H NMR of CMCS and its conjugate (CMCS-NC-1) (D2O, 25 ◦C).
porated NC content. In contrast, CMCS-NC-1 hydrogel with a high
NC content has a lower SD than CMCS-NC-2 hydrogel with a low
NC content. It is clear that the irradiation time and incorporated
NC content affect the network structure of the resultant hydro-
gel. A longer irradiation time or higher NC content would result in
the formation of a denser hydrogel network with a lower swelling
degree.
boxymethyl group) (Wang et al., 2007), but also the additional
proton peaks of incorporated NC groups at 6.72 ppm (CH CH–CO),
7.53 ppm (Ar–CH CH), 7.71 and 8.14 ppm (H–Ar). These results
confirmed the formation of an amide linkage between the primary
amino groups of CMCS and the carboxyl groups of NHS-NC.
Fig. 3 shows the gelation efficiency (GE) as a function of irradia-
tion time for aqueous solutions of CMCS-NC samples upon exposure
to 365 nm radiation in the absence of photoinitiator. With the
increase of irradiation time, the GE was found to have an obvi-
ous improvement. When the irradiation time increased from 20
to 60 min, for example, the GE of aqueous CMCS-NC-1 solution
increased from 29.6 1.4% to 78.5 3.9%, and the GE of aqueous
CMCS-NC-2 solution increased from 9.1 0.5% to 35.0 1.7%. This
implies that an increase of the irradiation time will be favorable
for the photogelation. In comparison with 5.0% aqueous solution
of CMCS-NC-2 incorporated with a low nitrocinnamate (NC) con-
tent (DS = 1.9), 5.0% aqueous solution of CMCS-NC-1 incorporated
with a high NC content (DS = 11.2) has a higher GE value, indicating
the contribution of the incorporated NC groups to the UV-induced
gelation. Fig. 4 gives the swelling degree (SD) as a function of irra-
diation time for the hydrogels formed from 5.0% aqueous solutions
of CMCS-NC samples upon exposure to 365 nm radiation in the
absence of photoinitiator. On prolonging the irradiation time, the
SD was found to have an obvious decrease irrespective of incor-
This gelation phenomenon of aqueous CMCS-NC solution upon
exposure to 365 nm irradiation in the absence of photoinitiator
may be caused by the intermolecular cycloaddition formation
(crosslinking) of the incorporated NC groups under the photoir-
radiation and subsequent network structure formation, as shown
in Fig. 5. To confirm this hypothesis, UV–vis absorbance of aque-
ous CMCS-NC solution during UV irradiation was determined, as
indicated in Fig. 6. Before UV light irradiation (irradiation time = 0),
aqueous CMCS-NC solution exhibits an absorption maximum at
314 nm due to the incorporated NC groups. Upon exposure to the
near-visible–UV light (365 nm), the absorbance peak at 314 nm
underwent a hypsochromic shift and a decrease in its inten-
sity. Within 20 s of irradiation, this maximum absorbance peak
decreased its intensity by approximately 16% and blue-shifted
about 5 nm. Although at a slower rate, this trend continued with
irradiation time. A similar response has been reported for other
cinnamate derivatives when incorporated into polymeric materi-
als, and it was found to be the result of cis–trans isomerization and
photodimerization reactions (Lee et al., 2003; Yuan et al., 2005). In
this case, the NC moieties were covalently bonded to adjacent NC
moieties by forming the cyclobutane ring via the photocycloaddi-
tion reaction, which could act as crosslinking points and result in
the formation of hydrogel network structure. Obviously, a greater
number of crosslinking points, which may be induced by a higher
NC content or a longer irradiation time, would lead to a higher GE
and make the photocrosslinked hydrogel to have a lower SD value.
Further work was dealt with the rheological characterization of
aqueous CMCS-NC system before and after photoirradiation. Fig. 7
gives the angular frequency dependence of storage modulus (Gꢀ)
and loss modulus (Gꢀꢀ) for 5.0% aqueous CMCS-NC-1 solution before
and after UV irradiation for 30 min in the absence of photoinitiator
and corresponding optical photos for their flow states. As seen, the
system before the irradiation was in sol state, and showed the vis-
coelastic behavior with dominating viscous property. In particular,
the Gꢀ and Gꢀꢀ values were too small to be measured accurately in the
low frequency region. In contrast, the system after the irradiation
was in gel state, and the Gꢀ value was observed to be consider-
ably greater than the Gꢀꢀ value over the entire range of frequency.
Fig. 3. The gelation efficiency as a function of irradiation time for 5.0% aqueous
solutions of CMCS-NC samples upon exposure to 365 nm radiation in the absence of
photoinitiator.

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R. Hu et al. / International Journal of Pharmaceutics 393 (2010) 96–103
Fig. 5. A possible mechanism for the photogelation of aqueous CMCS-NC solution.
Moreover, the Gꢀ value is fairly constant throughout the entire
frequency region, although a slight increase is observed with the
increase of frequency. These phenomena indicate that the system
after the irradiation displays a predominantly solid like behavior,
which can be attributed to the UV-induced crosslinking. In addition,
the incorporated NC content has a great influence on the mechan-
ical strength of the resultant CMCS-NC hydrogel. We investigated
the storage modulus as a function of frequency for two CMCS-NC
hydrogels incorporated with various NC contents (Fig. 8), and found
that CMCS-NC-1 hydrogel with a high NC content had a higher Gꢀ
value in the entire frequency region when compared to CMCS-NC-2
hydrogel with a low NC content. This may be due to the formation of
a denser network structure in CMCS-NC-1 hydrogel. We carried out
the SEM observation for the structural morphology of two CMCS-NC
hydrogels and confirmed such a deduction (Fig. 9).
For the resultant CMCS-NC-1 and CMCS-NC-2 hydrogels, their
in vitro degradation was evaluated in 4 mg/mL lysozyme solution
of pH 7.4 at 37 ◦C, as shown in Fig. 10. In general, natural polysac-
charides including chitosan and chitin are degraded by enzymatic
hydrolysis (Amano and Ito, 1978; Pangburn et al., 1982). In this
study, we found that two chitosan-based hydrogels had also a
biodegradation property. As seen, both of two hydrogels lost weight
during the degradation period. In contrast, CMCS-NC-2 hydrogel
incorporated with a low nitrocinnamate content had a faster degra-
dation rate due to its looser network structure (Fig. 9). In this case,
a lower crosslink density of CMCS-NC-2 hydrogel allows for more
ready access of the enzyme to the chitosan backbone. Moreover, the
penetration of the enzyme into the hydrogel bulk would increase
as the crosslink density decreased. Both of these effects would
increase the rate of biodegradation.
To explore their drug delivery application, two CMCS-NC hydro-
gels loaded with doxorubicin hydrochloride (DOX, an anticancer
drug) during their formation were investigated for the in vitro drug
Fig. 6. UV–vis absorbance of aqueous CMCS-NC solution with a concentration of
0.24 mg/mL during UV irradiation at ꢀ = 365 nm (irradiation time, 0–1200 s).

R. Hu et al. / International Journal of Pharmaceutics 393 (2010) 96–103
101
Fig. 7. Dynamic storage and loss moduli of 5.0% aqueous CMCS-NC-1 solution before and after UV irradiation (365 nm, 30 min, room temperature) in the absence of
photoinitiator and corresponding optical photos for their sol and gel states.
release behavior. Fig. 11 gives the cumulative DOX release against
time for each hydrogel sample in a pH 7.4 phosphate-buffered
saline at 37 ◦C. As seen, there is a sustained release behavior in
these cases. For example, CMCS-NC-1 hydrogel released only about
30.5% of the loaded DOX in the first 5 h and another 17.1% in 20 h,
while CMCS-NC-2 hydrogel released only about 35.4% of the loaded
DOX in the first 5 h and another 25.2% in 20 h. In contrast, the
DOX-loaded CMCS-NC-1 hydrogel has a slower release rate due to
the effect of its higher crosslink density on the drug diffusion. The
relatively low amount of DOX released from two CMCS-NC hydro-
gels was probably related to the stronger interactions between the
hydrogel matrix and DOX. To understand the release mechanism of
the entrapped DOX molecules from the CMCS-NC hydrogels, we fit-
ted the release curves using the following semi-empirical equation
(Korsmeyer et al., 1983):
Mt
= ktn
(3)
M
∞
where k is the kinetic constant and n is an exponent character-
izing the diffusional mechanism, Mt and M are the cumulative
∞
amount of the drug released at t and equilibium, respectively. Only
in two cases of n = 0.5 (pure diffusion controlled drug release) and
n = 1 (swelling-controlled drug release or Case II transport), Eq. (3)
becomes physically realistic. Other values for n indicate anoma-
lous transport kinetics (Ritger and Peppas, 1987). In this study,
the n value was obtained to be 0.45 0.02 with the determination
coefficient (R) of 0.986 for the DOX-loaded CMCS-NC-1 hydrogel,
and 0.53 0.03 with the determination coefficient (R) of 0.988
Fig. 8. Storage modulus as a function of frequency for two CMCS-NC hydrogels
incorporated with various NC contents.

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R. Hu et al. / International Journal of Pharmaceutics 393 (2010) 96–103
Fig. 9. SEM photos of two CMCS-NC hydrogels incorporated with various NC contents.
for the DOX-loaded CMCS-NC-1 hydrogel, respectively. It seems
that the diffusion behavior of the entrapped DOX from the pho-
tocrosslinked CMCS-NC hydrogels belongs to anomalous transport
kinetics.
4. Conclusion
In this study, chitosan was hydrophilically modified by car-
boxymethylation to increase its water solubility, and then used
for the conjugation with 4-nitrocinnamate acid. This prepara-
tion process results in a novel polysaccharide derivative capable
of UV photogelation in the absence of photoinitiator or catalyst.
The unique gelation ability of this modified polysaccharide could
be attributed to the intermolecular cycloaddition formation of
the incorporated nitrocinnamate groups and subsequent network
structure formation. It was found that the photoirradiation time
and incorporated nitrocinnamate content affected greatly the gela-
tion efficiency of the modified polysaccharide and the swelling
degree of the resultant hydrogel in water. Moreover, a relatively
high nitrocinnamate content could make the photocrosslinked
hydrogel to have a denser network structure, a greater mechanical
strength, a slower biodegradation and drug release rate.
Acknowledgments
This work is supported by the NSF of China (20874116,
20676155 and J0730420) and the NSF of Guangdong Province in
China (8151027501000004 and 9151027501000105) as well as
the Doctoral Research Program of Education Ministry in China
(20090171110023).
Fig. 10. In vitro biodegradation of two CMCS-NC hydrogels incorporated with vari-
ous NC contents in 4 mg/mL lysozyme solution of pH 7.4 at 37 ◦C.
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