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International Journal of Biological Macromolecules xxx (2017) xxx–xxx

Contents lists available at ScienceDirect

International Journal of Biological Macromolecules

journal homepage: www.elsevier.com/locate/ijbiomac

Development of a gallic acid-loaded chitosan and polyvinyl alcohol

hydrogel composite: Release characteristics and antioxidant activity
T. Thanyacharoen a , P. Chuysinuan b , S. Techasakul b , P. Nooeaid c , S. Ummartyotin a,∗
a
Materials and Textile Technology, Faculty of Science and Technology, Thammasat University, Patumtani, Thailand
b
Laboratory of Organic Synthesis, Chulabhorn Research Institute, Bangkok, Thailand
c
Faculty of Agricultural Product Innovation and Technology, Srinakharinwirot University, Thailand

a r t i c l e i n f o a b s t r a c t

Article history: The physico-chemical properties of a chitosan and polyvinyl alcohol (CS/PVA)-based hydrogel compos-
Received 25 May 2017 ite were investigated. Tetraethyl orthosilicate (TEOS) was employed as a crosslinking agent. The results
Received in revised form 30 August 2017 indicated that the chitosan-based composite presented a thermal resistance up to 200 ◦ C. The struc-
Accepted 1 September 2017
tural properties, which were evaluated using FTIR and DSC, showed good miscibility between chitosan
Available online xxx
and polyvinyl alcohol. SEM presented a compact and homogeneous structure. The release profile of the
chitosan-based hydrogel composite was investigated using gallic acid (GA). It showed high antioxidant
Keywords:
activities, which were monitored using DPPH radical scavenging. Diffusion of water into the chitosan-
Chitosan
Polyvinyl alcohol
based hydrogel was assumed to be pseudo-Fickian in PBS solution. The CS/PVA-based hydrogel composite
Drug release exhibited good properties as a drug delivery system.
Gallic acid © 2017 Elsevier B.V. All rights reserved.

1. Introduction strongly considered as the most efficient technique for sustainable

With the exponential growth of the worldwide population, the
development of industrial technology was researched to fulfill
the requirement of human welfare. The role of industrial tech-
nology was developed from lab-scale research to the industrial
sector. From the fundamental point of view, numerous technology
approaches are versatile and are used in the food and beverage,
medical research, infrastructure, electronic devices and automo-
tive industries. Although, the existence of technology offers many
benefits for quality of life and welfare, it may result in waste and
hazardous products, which are difficult to manage. Therefore, to
solve this issue, many environmental policies are strictly encour-
aged. The concept of policy may involve the utilization of chemical
reagents and hazardous products on a controllable scale. This con-
cept was employed in many research studies and product lines.
However, the concept of green technology is very challenging. It
is considered an alternative technique for solving environmental
issues [1–4]. Moreover, it is remarkable to note that the properties
of biomaterials have gained significant interest. Biomaterials offer
high mechanical properties, high chemical resistance, high thermal
stability and good optical properties. Utilization of biomaterials was
∗ Corresponding author.
E-mail address: sarute.ummartyotin@gmail.com (S. Ummartyotin).
development. Up to now, many biomaterials have been developed
such as cellulose and its derivatives, chitin and chitosan, poly lactic
acid, and starch.
To our knowledge, chitosan (CS) was considered a natu-
rally occurring biopolymer. It was commercially produced via
deacetylation of chitin. From the structural point of view, chi-
tosan was described as a linear polysaccharide composed of
randomly distributed ␤-(1 → 4) linked d-glucosamine and N-
acetyl-d-glucosamine [5–9]. It was produced by treating the chitin
shells of shrimp and other crustaceans with an alkaline substance.
Utilization of chitosan provided many advantages such as low
toxicity, a high level of biocompatibility and assistance in cell
attachment, proliferation and non-antigenicity. Currently, due to
many benefits, the use of chitosan has gained significant interest
for development in food technology, medical and pharmaceuti-
cal research. One of the most challenging research aspects for
chitosan was focused on hydrogel formation [10–13]. From the fun-
damental point of view, a hydrogel’s physicochemical properties
can be altered in response to external stimuli. Due to the existence
of certain functional groups along the polymeric chain, a hydro-
gel can be changed by temperature, pH, enzyme and even ionic
strength. Subsequently, this resulted in the utilization of hydrogels
in many diverse applications such as drug delivery systems, arti-
ficial muscle, gene delivery systems, immobilization of enzyme,
food technology and cosmetic applications [14–16]. To form a

http://dx.doi.org/10.1016/j.ijbiomac.2017.09.002
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hydrogel composite, polyvinyl alcohol (PVA) was considered as the
matrix phase. The water absorbing capacity of polyvinyl alcohol
is 5–10 times its weight. It was commonly employed in the food,
medicine and chemical industries. It provided many excellent prop-
erties such as gel properties, water holding capacity, film formation
and foaming ability [17]. Chitosan and polyvinyl alcohol crosslink
with TEOS, which is a non-toxic and biocompatible crosslinker
that easily binds via condensation reactions in comparison with
previously reported crosslinkers (glutaraldehyde, epichlorohydrin,
borate and tripolyphosphate) [18]. Islam et al. have reported the
use of TEOS for synthesizing a pH sensitive chitosan and polyvinyl
alcohol blend for controlled drug delivery application [19]. TEOS or
a silane crosslinker are suitable for enhanced interfacial adhesion
and improved mechanical properties of composite materials due to
the reaction of Si-O bonds in TEOS, which reacted with an amino
group in a chitosan polymer.
Therefore, to evaluate the chitosan-based hydrogel
as a controlled-release material, gallic acid (GA, 3, 4, 5-
trihydroxybenzoic acid) was employed as a bioactive compound. It
is considered an antioxidant and is commonly found in a variety of
fruits and vegetables, for example, in tea leaves, grapes, cherries,
and longan seeds. From the structural point of view, GA is consid-
ered as a trihydroxybenzoic acid, which is commonly employed in
health science research [20]. It is a natural phenolic antioxidant,
which is extractable from natural products. It has been reported
that GA has anti-allergic, anti-inflammatory, anti-mutagenic
and anti-carcinogenic activity [21]. Furthermore, de Rosa et al.
prepared chitosan-containing GA via the lyophilization method
to enhance antioxidant activities [22]. Chitin hydrogel-loaded
GA provided wound healing, and anticancer activity was studied
[23]. To integrate chitin into a CS/PVA-based hydrogel composite,
chitosan was conjugated with GA to provide water solubility,
water swelling property, and antioxidant activity to the chitosan
hydrogel using a crosslinking agent [24].
Controlled release systems maintain the drug concentration in
the blood or in target tissues at a desired value as long as possible.
Normally, initially, the controlled release system rapidly releases
a drug. Then, the drug release kinetics follows a release behavior
to supply the maintenance dose, which enables the attainment of
a desired drug concentration. The Higuchi and Korsmeyer-Peppas
model was used to detect the mechanism of drug release. This
model is represented by the equation Mt /M∞ = Ktn , where Mt /M∞
is the fraction of drug release at time t, K is the release rate con-
stant, and n is the release exponent. The n value is used to predict
the release mechanism of the drug. A value of 0.45 ≤ n corresponds
to the Fickian diffusion mechanism, that of 0.45 < n < 0.89 to non-
Fickian transport, n = 0.89 to case II transport, and n 䊐 0.89 to super
case II transport.
The objective of this research work is to encapsulate GA, as a
model phenolic compound, in a CS/PVA-based hydrogel composite
using a conventional synthetic route. The physicochemical proper-
ties of the hydrogel were investigated. In addition, the antioxidant
capacities and release characteristics of the encapsulated GA were
measured.
2. Experimental
2.1. Materials
Chitosan (medium molecular weight, 75–85% degree of deacety-
lation) and polyvinyl alcohol (molecular weight 4000 g/mole) were
purchased from Sigma Aldrich, Co, ltd. They were employed as
starting chemical reagents. Tetraethyl orthosilicate (TEOS) was
purchased from Sigma Aldrich, Co, ltd. Phosphate buffered saline
(PBS) was purchased from VWR Cief Science Amresco, LLC. These
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compounds were employed as a crosslinking agent and a buffer
solution, respectively. Acetic acid was purchased from Labscan Asia
Co., ltd. All chemical reagents were used as received without further
purification.
2.2. Methods
2.2.1. Preparation of a chitosan and polyvinyl alcohol-based
hydrogel composite
A chitosan and polyvinyl alcohol (CS/PVA)-based hydrogel com-
posite was prepared via wet conventional synthesis. The amount of
chitosan that was added to the CS/PVA hydrogel (9:1 to 5:5 ratios)
was coded as CS/PVA 9:1, CS/PVA 8:2, CS/PVA 7:3, CS/PVA 6:4 and
CS/PVA 5:5. Briefly, chitosan was dissolved in acetic acid (1% v/v) at
room temperature for 3 h to ensure solubility. In parallel, polyvinyl
alcohol was dissolved in DI water (10% w/v). Then, the chitosan
solution was poured into the polyvinyl alcohol solution. In total,
2 ml of TEOS was added to the mixture. The solution was stirred at
70 ◦ C for 3 h to obtain a homogeneous gel. After that, the gel was
casted onto a petri dish and dried in an oven at 70 ◦ C. To load GA
into the CS/PVA composite hydrogel, which is coded as GA-CS/PVA,
GA was loaded into a CS/PVA solution in the amount of 20%wt based
on the polymer solution, coded as GA-CS/PVA 9:1, GA-CS/PVA 8:2,
GA-CS/PVA 7:3, GA-CS/PVA 6:4 and GA-CS/PVA 5:5. The solution
was stirred at 70 ◦ C for 3 h to obtain a homogeneous gel. Then, the
gel was casted onto a petri dish and dried in an oven at 70 ◦ C.
2.2.2. Swelling properties of the hydrogel composite
The CS/PVA-based composite was investigated for swelling
behavior. In this study, the gravimetric technique was employed
to determine the swelling and equilibrium data of the hydrogel.
It was immersed in DI water for 48 h. After an appropriate time
interval, specimens were removed from the solution, dried with a
filter paper to remove excess water, and were measured. Five sam-
ples were investigated, and the data were reported as the statistical
average and standard deviation. The swelling ratio was determined
as follows [Eq. (1)]:
Q(g/g) = (Wwet − Wdry )/Wdry (1)
where Wwet is the weight of a swollen hydrogel at submersion time,
and Wdry is the initial weight of the dry hydrogel.
2.2.3. DPPH radical scavenging activity of gallic acid-loaded
chitosan/PVA hydrogels
The DPPH radical scavenging activity of GA-CS/PVA hydrogels
was determined using the method developed by Chuysinuan et al.
[26]. Briefly, each specimen with a 2.5-cm diameter round shape
was first extracted in 10 ml of methanol and then shaken in a water
bath for 1 h. An aliquot of the sample was diluted with 10 ml of
methanol. The reaction mixture consisted of 1.0 ml of the sample
and 3.0 ml of the DPPH radical solution (0.1 mM in methanol). The
absorbance of the reaction mixture, which was protected from light,
was measured after 30 min. The mixture was incubated for 30 min
in the dark at ambient temperature. The absorbance was measured
using a microplate reader at 517 nm. The % scavenging activity was
calculated according to the following equation [Eq. (2)]:
%scavenging = [(Abs.Blank − Abs.Sample)/Abs.Blank] × 100 (2)
2.2.4. In vitro release study
The cumulative amount of released GA from GA-CS/PVA hydro-
gels was measured using immersion methods. The specimens
(2.5 cm in diameter, circular shape) were individually immersed
in 30 ml of a phosphate buffer solution (PBS buffer) at 37 ◦ C for
4320 min. The sample solution (1 ml) was withdrawn at submer-
sion time intervals, and an equal amount of fresh release medium
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was added. The cumulative release of GA in PBS buffer was calcu-

lated according to the calibration curve and reported as the average
values ± standard deviation. The measurements were performed in
triplicate.

2.2.5. Degradation and stability analysis

Degradation studies of the GA-CS/PVA hydrogel were performed
in a humidity chamber (45 ◦ C, 75% RH). The samples were weight
every 5 days until day 15. The weight was recorded as a function of
degradation time and compared with the initial weight.
A stability analysis of gallic acid-loaded chitosan and polyvinyl
alcohol hydrogels was performed according to the procedure
described by P. Chuysinuan et al. [25,26]. The% remaining of gallic
acid-loaded chitosan and polyvinyl alcohol hydrogel was investi-
gated based on the following equation:

Remaininggallicacid(%) = (W/Wi) × 100 (3)

Fig. 1. FTIR spectra of the CS/PVA-based hydrogel composite.

2.3. Characterization

2.3.1. Thermogravimetric analysis

The thermal degradation behavior of the CS/PVA-based hydrogel
composite was characterized using TGA (TGA Q500, TA Instru-
ments). In total, 20 mg of the sample was heated from room
temperature to 700 ◦ C in N2 at a heating rate and a flow rate of
5 ◦ C/min and 70 ml/min, respectively.
2.3.2. Scanning electron microscopy
The CS/PVA-based hydrogel composite was investigated using
SEM (SEM, Quanta 250 microscope, Japan). The specimens were
gold-coated using a sputtering device (Jeol, JFC-1200) prior to the
SEM observation. A magnification of 4500 × was used.
2.3.3. UV–vis spectroscopy
A Varian Cary 5000 UV–vis NIR spectrophotometer (Agilent
Technologies, CA, USA), equipped with a transmittance accessory,
was employed to record the electronic spectrum of the samples
in the wavelengths of 200–900 nm. This technique allowed the
absorbance spectra of the samples to be studied. The accessory
consisted of a 110-nm diameter integrating sphere and an in-built
high-performance photomultiplier. Each sample was placed in a
sample cell, which was specifically designed for the instrument. A
baseline was recorded and calibrated using a polytetrafluoroethy-
lene (PTFE) reference cell.
2.3.4. Fourier transform infrared spectroscopy
FTIR spectra were recorded using a Fourier transform infrared
spectrometer (PerkinElmer, USA). Spectra were measured at room
temperature in the spectral range from 4000 to 400 cm−1 with a
resolution of ± 4 cm−1 and a scan frequency of 32 times.
2.3.5. Atomic force microscopy
AFM was performed using a Digital Instruments Nanoscope III
Scanning Probe Microscope (Digital Instruments, CA, USA) under
ambient conditions (22 ◦ C, 45–55% relative humidity) over an area
of 10 ␮m × 10 ␮m. The CS/PVA-based hydrogel composites were
prepared as thin, flat sheets. The instrument was equipped with
a silicon nitride tip and operated in the lateral contact mode. The
measurements were repeated five times for comparable topological
analysis.
2.3.6. Differential scanning calorimetry
DSC of the CS/PVA-based hydrogel composite was performed
from room temperature to 300 ◦ C at a heating rate of 10 ◦ C/min with
a TA-10000 DSC (TA Instruments, DE, USA). The glass transition
temperature, melting temperature, and specific heat capacity were
determined from the heat flow curve.
3. Results and discussion
3.1. Physico-chemical properties of the chitosan and polyvinyl
alcohol-based hydrogel composite
The chitosan-based hydrogel composite was successfully syn-
thesized via the wet conventional synthetic route. The hydrogel
was malleable and easily shaped at ambient temperature without
any external stimuli. FTIR spectra of the CS/PVA-based hydrogel
composite are exhibited in Fig. 1. The neat chitosan and polyvinyl
alcohol film spectra are provided for comparison. It was remark-
able to note that neat polyvinyl alcohol exhibited a broad peak at
3500–3600 cm−1 due to OH stretching. The characteristic peaks
at 2850 cm−1 , 1400 cm−1 and 1100 cm−1 were attributed to CH
stretching, CH bending and CO stretching, respectively. In the
case of the hydrogel composite, the existence of chitosan presented
amide I and amide II peaks. The absorption peaks were at 1650 cm−1
and 1080 cm−1 , respectively. These characteristic peaks are consis-
tent with the previous literature, as suggested by Fan et al. [27].
Furthermore, it is important to note that the characteristic peak
of the hydrogel composite is apparent as the broad band in the
3000–3500 cm−1 range. This region corresponds to the stretching
vibrations of hydrogen bonded OH and NH, and the peaks are
clearly shifted to lower wavenumbers. This phenomenon was due
to the crosslinking reaction between the hydrogel composite and
TEOS.
In particular, morphology and roughness were considered as
some of the most important parameters for the control and release
characteristics of GA from the CS/PVA-based hydrogel compos-
ite. Microstructure and roughness were considered as important
parameters of a hydrogel, as suggested by Munz et al. [28].
The AFM technique was employed to investigate the rough-
ness properties of the hydrogel-based composite. Therefore, the
inhomogeneous structure of chitosan and polyvinyl alcohol was
evaluated. Figs. 2 and 3 present the AFM micrograph and rough-
ness evaluation of the CS/PVA-based hydrogel composite. In Fig. 2,
the roughness of the hydrogel remained in a similar region. Due
to the existence of chitosan in the hydrogel composite, the rough-
ness slightly increased, which may affect the release mechanism
process. When a hydrogel swells in solvent media, a higher rough-
ness may enable a higher surface area for reaction. The efficiency
of the release mechanism may consequently be high with respect

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Fig. 2. AFM micrographs of the CS/PVA-based hydrogel composite.

to roughness. The average topography roughness was estimated to
be 0–40 nm, as indicated in Fig. 3.
Fig. 4 presents the thermal decomposition characteristics of the
CS/PVA hydrogel composite. The weight loss can be categorized
into three regions. Weight loss was observed when the composite
was heated from room temperature to 300 ◦ C. This was related to
water and solvent evaporation. However, due to the high amount
of chitosan, the hydrogel was highly stable. This led to an increase
in the intermolecular spaces between the chitosan chain and PVA,
which subsequently decreased the H-bond interactions between
the chains as suggested by Martins A.F. et al. [29]. With the increase
of temperature to 300–500 ◦ C, the decomposition of both chitosan
and PVA occurred. The role of chitosan can be attributed to the
more intra- and intermolecular H-bonding interactions between
chitosan and PVA. It is involved in the reaction between the amine
group of chitosan and the hydroxyl group of PVA. This discussion
was strongly consistent with a previous publication of Mohamed
R.R. et al. [30]. However, it can be implied that due to the pres-
ence of TEOS, crosslinking between chitosan and PVA was formed.
This may provide good thermal stability. Moreover, above 500 ◦ C,
decomposition was terminated. The hydrogel composite presented
as a char and a residual.
To evaluate the thermal properties of the hydrogel, DSC mea-
surements were employed to investigate the thermal behavior
of the chitosan-based hydrogel composite. From the fundamen-
tal point of view, both chitosan and PVA provide a strong affinity

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Fig. 3. Topography of the CS/PVA-based hydrogel composite.

for water. They were easily hydrated, as suggested by Kammoun
et al. [31]. Fig. 5 shows the endothermic peak associated with the
helix-coil transition. The glass transition temperature and melting
temperature were estimated to be 80 and 220 ◦ C, respectively. The
role of the glass transition temperature was considered to be an
important criterion for evaluating the miscibility, as suggested by
Jridi et al. [32]. Therefore, in the completely miscible film of chitosan
and PVA, only one glass transition temperature was observed. In the
case of the composite, the miscible blend was obtained. The glass
transition temperature was close to that of the neat polyvinyl alco-
hol. It was slightly shifted to a lower value close to that of neat
chitosan. This had a similar trend in order of magnitude to the
chitosan content. In the CS/PVA-based hydrogel composite, when
the chitosan content increased, the glass transition temperature
increased. The increase of the glass transition temperature indi-
cated some level of blending after molecular interaction between
chitosan and PVA. This discussion was strongly associated with
Abureesh et al. [33].
3.2. Swelling behavior, antioxidant activity and release
characteristic of gallic acid from the chitosan and polyvinyl
alcohol-based hydrogel composite
The swelling ratio of the CS/PVA-based hydrogel composite was
investigated. From the fundamental point of view, the swelling
properties were considered an important property of hydrogels

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Fig. 4. Thermal decomposition of the CS/PVA-based hydrogel composite. Fig. 6. Swelling behavior and percent of weight loss of the CS/PVA-based hydrogel
composite.

Fig. 5. DSC thermogram of the CS/PVA-based hydrogel composite.

Fig. 7. Antioxidant activity of GA in the GA-CS/PVA-based hydrogel composite.

to demonstrate the possible uptake of liquids. These properties

were employed in a drug delivery system. It was important to note
that swelling properties were described in% swelling, which was
directly proportional to the water amount that was taken up by the
hydrogel. The diffusion mechanism was influenced by the embed-
ded water. Fig. 6 shows the swelling behavior of the composite as
a function of time. The behavior for PVA is provided for compari-
son. Due to the existence of chitosan in the composite, the swelling
behavior was decreased, as suggested by Huber et al. [34]. This phe-
nomenon occurred because it was difficult for chitosan powder to
be adsorbed in DI water media. This may have occurred because the
amino groups in the polymeric structure were not charged when
DI water was used as the swelling medium. Compared with PVA,
OH groups were dissolved in DI water, which led to electrostatic
repulsion between the polymer chains. In the case of CS/PVA 5:5,
only a 30% swelling was observed. This may imply high dimensional Fig. 8. Cumulative release of GA from the GA-CS/PVA-based hydrogel composite.
stability.
Furthermore, investigation of an antioxidant assay was con- duce free radicals, which leads to chain reactions that may damage
ducted. This is promising for extending the GA-CS/PVA-based cells [35,36]. Fig. 7 shows the DPPH radical scavenging capacity
hydrogel composite to drug delivery systems. The antioxidant of the GA-CS/PVA-based hydrogel composite. The activity was very
activity of the GA-CS/PVA-based hydrogel composite, which was high, and it subsequently decreased with the integration of chitosan
monitored using the free radical-scavenging activity, was inves- in the hydrogel composite. The decrease in antioxidant proper-
tigated. From the fundamental point of view, an antioxidant was ties can be explained by many reasons. Specifically, it was due to
therefore considered as a molecule that inhibits oxidation of other the lower solubility of the hydrogel composite compared with GA-
molecules. Oxidation is involved in chemical reactions that can pro- CS/PVA. It is remarkable to note that our results are consistent with

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the previous publication of Xue et al. [37]. The existence of chitosan

can have a chelating action on metal ions. PVA has an important
role as an electron and hydrogen donor. These species can subse-
quently react with free radicals and convert to more stable products
or terminate the radical chain reaction.
The release characteristics of GA from the GA-CS/PVA-based
hydrogel composite are presented in Fig. 8. GA is considered to
be a model drug to study the release mechanism [38]. The release
of GA begins when the chitosan-based hydrogel is in contact with
an aqueous medium. Water diffuses in and dissolves the drug. It
is clear that the release characteristic is dependent on chitosan,
which was used to design the hydrogel. For CS/PVA 5:5, the release
of GA was 18% after 72 h. This suggests that the composition of
chitosan plays an important role in the release properties of the
hydrogel. It is notable that with a higher chitosan concentration,
the hydrogel was suitable for the release of GA. A higher chitosan
content led to lower swelling properties, as suggested by Tang et al.
[39].

3.3. Degradation and stability analysis

The degradation of GA-CS/PVA hydrogels was evaluated, and

the results are shown in Fig. 9a). The results showed that the%
degradation values of GA-CS/PVA 9:1, GA-CS/PVA 8:2, GA-CS/PVA
7:3, GA-CS/PVA 6:4, and GA-CS/PVA 5:5 were only 87.38 ± 6.44,
95.59 ± 1.67, 98.21 ± 0.48, 92.38 ± 3.45, and 97.59 ± 0.83, respec-
tively after 15 days. To further confirm the stability of GA in
GA-CS/PVA, the hydrogels were subjected to humid condition for
0, 5, 10, and 15 days. The% remaining and antioxidant activity of GA
were determined under humid conditions. Our results showed that
the content of GA was 74.81 ± 4.81 and 70.93 ± 0.93 in GA-CS/PVA
9:1, 73.28 ± 4.19 and 71.51 ± 0.77 in GA-CS/PVA 8:2, 71.34 ± 3.45
and 70.93 ± 0.82 in GA-CS/PVA 7:3, 68.17 ± 3.76 and 70.54 ± 3.76
in GA-CS/PVA 6:4, and 70.67 ± 2.36 and 72.48 ± 0.69 in GA-CS/PVA
5:5 after 15 days of storage. Similar results were observed for the
antioxidant activity of the GA-CS/PVA hydrogels. The% radical scav-
enging activity was observed to be in the range of 70–79%, as
shown in Fig. 9c). It was noted that the GA-CS/PVA hydrogels were
not significantly degraded and showed high antioxidant activity of
70–79%.

4. Conclusion

In the present report, we demonstrated the physico-chemical

properties of the CS/PVA-based hydrogel composite. TEOS was
employed as a crosslinking agent. Characterization of the thermal,
morphological, structural and surface properties of the CS/PVA-
based composite was performed. GA was employed as a bioactive
agent. It exhibited excellent antioxidant properties. The release
profile of the chitosan-based composite was investigated in phos-
phate buffer solution. The release profile was assumed to follow
the pseudo-Fickian model. Degradation and stability studies of
GA-CS/PVA showed the remaining amount of GA under humid con-
dition after 15 days. In addition, it was remarkable to note that the
CS/PVA-based hydrogel composite exhibited good properties for
use in a drug delivery system.

Fig. 9. % Degradation (a), stability (b) and antioxidant activity (c) of GA in the GA-
CS/PVA-based hydrogel composite.
Acknowledgments
The authors would like to acknowledge the financial support
provided by Thammasat University. We are grateful for the space
and research facilities support by the Chulabhorn Research Insti-
tute. We would like to thank Mr. Nitirat Chimnoi for research
facilities support and Ms. Kittiporn Trisupphakant for assisting with
the film characterization.

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