Radiation Physics and Chemistry 74 (2005) 2630

Synthesis and characterization of thermo- and pH- sensitive

hydrogels based on Chitosan-grafted N-isopropylacrylamide
via g-radiation
Hong Cai
a
, Zheng Pu Zhang
a,
, Ping Chuan Sun
a
, Bing Lin He
a
, Xiao Xia Zhu
a,b
a
State Key Laboratory of Functional Polymeric Materials for Adsorption and Separation, Tianjin, 300071, China
b
Departement de chimie, Universite de Montreal, C.P. 6128, Succursale Centre-ville, Montreal, QC, Canada H3C 3J7
Received 30 September 2004; accepted 12 October 2004
Abstract
Thermo- and pH-sensitive hydrogels were prepared by graft copolymerization of chitosan (CS) and N-
isopropylacrylamide via g-radiation. The effects of monomer concentration and irradiation dose on grafting percentage
and grafting efciency were studied. The graft copolymers were characterized by
13
C CP/MAS NMR and
thermogravimetric analysis. The pH and thermosensitivity and swelling properties of the hydrogels were investigated.
The results showed that the grafting percentage and grafting efciency increased with the increase of monomer
concentration and total irradiation dose. The highest grafting percentage is 620%, the lower critical solution
temperature (LCST) of this hydrogel is about 28 1C.
r 2004 Elsevier Ltd. All rights reserved.
Keywords: Chitosan; N-isopropylacrylamide; Thermo- and pH-sensitive; Graft; g-radiation
1. Introduction
Hydrogels are crosslinked, three-dimensional hydro-
philic polymer networks, which swell but do not dissolve
when brought into contact with water. Some hydrogels,
which sometimes undergo a volume change in response
to a change in surrounding conditions such as tempera-
ture (Hirokawa and Tanaka, 1984; Bae et al., 1990;
Zhang et al., 2002), pH (Park and Hoffman, 1992; Guan
et al., 1996; Chen and Hoffman, 1995), antigen (Miyata
et al., 1999), light (Suzuki and Tanaka, 1990) and certain
chemicals (Ishihara et al., 1984; Kokufata and Zhang,
1991; Holtz and Asher, 1997), etc. Poly-N-isopropyla-
crylamide (PNIPA) is the most widely studied thermo-
sensitive hydrogels. PNIPA in aqueous medium has its
lower critical solution temperature (LCST) at 32 1C. The
volume phase transition is reversible, which led to some
potential applications such as temperature sensors,
controlled drug-releasing devices, articial muscles,
and enzyme-activity control (Fang and Kawaguchi,
2002; Kurisawa et al., 2000; Bae et al., 1987; Liu et al.,
1993).
Chitosan (CS) is a natural cationic polymer obtained
from N-deacetylation of chitin [(14)-2-acetamiodo-2-
deoxy-d-glucose], which is the second most abundant
natural polymer on earth after cellulose. This poly-
saccharide is considered to be nontoxic, biodegradable,
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doi:10.1016/j.radphyschem.2004.10.007

Corresponding author. Tel.: +86 22 23505046;

fax: +86 22 23503510.
E-mail address: zhangzp@nankai.edu.cn (Z.P. Zhang).
and biocompatible.
O
HOH
2
C
NH
2
HO
O
n
1
2
3
4
5
6
Chitosan
It has been used as an anticoagulant, a wound-healing
accelerator, and drug delivery material (Caner et al.,
1998; Singh and Ray, 1994; Mima et al., 1983). CS
exhibits a pH-sensitive behavior as a weak polybase
due to the large quantities of amino groups on its
chain.
Graft copolymerization of vinyl monomers onto
CS can introduce desirable properties and enlarge the
eld of the potential applications by choosing various
types of side chains (Kumbar and Aminabhavi, 2003;
Shantha and Harding, 2002.; Wang et al., 2000; Kim
et al., 2000). In recent years, a number of initiator
systems have been developed to initiate grafting
copolymerization. Radiation graft copolymerization is
a well-established technique for producing polymeric
materials that combine the chemical and physical
properties of both the base polymer and the grafted
monomer (Singh and Ray, 1997; Zhai et al., 2000; Li et
al., 2003). In this work, hydrogels based on CS grafted
N-isopropylacrylamide were prepared by
60
Co g-radia-
tion, the effects of monomer concentration and irra-
diation dose on grafting percentage and grafting
efciency were studied. The pH- and thermosensitivity
and swelling properties of the polymers were also
investigated.
2. Experimental
2.1. Materials
CS was purchased from Qingdao Lizhong Chitosan
Co., Ltd. China. The viscosity-average molecular weight
was 97000 g/mol and the N-deacetylation degree was
85%. NIPA was synthesized by reacting acryloyl
chloride with isopropylamine. All other chemicals were
of analytical grade and were used without further
purication.
2.2. Graft polymerization
A series of CS-g-NIPA hydrogels were prepared in the
following procedures: pure CS (0.5 g) dissolved in 5%
aqueous acetic acid (25 ml) in a glass reaction bottle, the
monomer was added to the CS solution. Mohrs salt
(ammonium ferrous sulphate) was added to the mixture
to minimize homopolymerization during irradiation.
The solution was deoxygenated by purging with nitro-
gen for 30 mins. The sealed reaction bottles were
irradiated at a dose from 3 to 10 kGy. After irradiation,
the product was extracted with methanol in a Soxhlet
extractor for 48 h, in order to remove the unreacted
monomer, homopolymer and other impurities. The
hydrogel was dried at 40 1C in a vacuum oven overnight.
The grafting percentage (G %) and grafting efciency
(GE %) were dened as follows:
G% W
g
W
o
=W
o
100;
GE% W
g
W
o
=W
m
100;
where W
g
, W
o
and W
m
are the weights of grafted
copolymer, chitosan and monomer, respectively.
2.3. Characterization
2.3.1.
13
C CP/MAS NMR analysis
13
C CP/MAS NMR spectra were recorded on a
Varian UNITY plus 400 NMR spectrometer in solid
state at a frequency of 100.6 MHz for
13
C nuclei. Sample
was placed in a zirconia rotor (5 mm), the spinning rate
was set at 4.5 kHz at the magic angle, and
13
C chemical
shifts were referenced to external hexamethylbenzene.
2.3.2. Thermogravimetric analysis
Dynamic thermogravimetric analysis was carried out
with a NETZSCH TG209 thermogravimetric analyzer
from Germany. The experiments were performed at a
heating rate of 10 1C/min from room temperature to
600 1C.
2.3.3. Swelling measurement
Swelling of the hydrogel was determined gravimetri-
cally after immersing the grafted product in water for a
week, the surface of the hydrogel was wiped with lter
paper in order to remove the free water and weighed.
The swelling ratio was determined as
Swelling ratio W
s
=W
d
;
where W
s
and W
d
are the weights of swollen and dry
hydrogels, respectively.
2.3.4. Thermal and pH analysis
The hydrogel was ground to powder, passed through
a sieve of 100 mesh, immersed in water for a week. The
thermosensitivity was measured by turbidimetry ob-
served at l 500 nm at different temperatures.
The hydrogels were immersed in the buffers of various
pH values from 1 to 13 for a week. The pH sensitivity
was measured by swelling ratios in different pH buffers.
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H. Cai et al. / Radiation Physics and Chemistry 74 (2005) 2630 27
3. Result and discussion
3.1. Grafting characterization
3.1.1. Gravimetric estimation
The graft copolymerization was monitored gravime-
trically. After the extraction of the homopolymer, the
weight gain of CS gives strong evidence for the grafting
of NIPA onto CS.
3.1.2.
13
C CP/MAS NMR spectroscopy analysis
13
C CP/MAS NMR spectra of CS and grafted CS
were shown in Fig. 1. The peak assignments of
13
C
chemical shifts of CS were 53.4 (C2), 56.8(C6), 71.4 (C3,
5), 79.2 (C4), and 101.6 (C1) ppm respectively, which is
close to the previous NMR experimental result of CS
(Yoksan et al., 2001). Except for the signals of CS
denoted as c in Fig. 1, several new peaks denoted as d
in Fig. 1 were found at a range from 1045 ppm in
grafted CS, which should be assigned to aliphatic signals
of grafted PNIPA, this further conrms the grafting of
PNIPA onto CS. On the other hand, it is known that CS
molecule contains two reactive groups at C2 and C6
positions (Liu et al., 2001). The grafted CS showed
downeld shifts for both, which implies that the grafting
reaction may have taken placed on C2 and C6 positions.
In addition, we also noticed that all peaks in the grafted
CS were broadened as the result of the paramagnetic
effect of Fe
3+
of ammonium ferrous sulphate on the
13
C
NMR signals.
3.1.3. Thermogravimetric analysis
The thermograms of CS and grafted CS (PG 620%)
obtained at a heating rate of 10 1C/min under nitrogen
are shown in Fig. 2.
The thermogram of CS exhibits two distinct stages.
One is in the range of 40120 1C due to water loss and
decomposition of polymers of low molecular weights,
the other in the range of 220480 1C is ascribed to a
complex process including dehydration of the sugar
rings, depolymerization and decomposition of the
acetylated and deacetylated units of the polymer. The
differential thermogravimatric curve of the grafted CS
shows three degradation steps. For the grafted CS, the
second degradation stage starts at about 210 1C which is
lower than that of CS. In the third stage of degradation
in the range of 370480 1C, the grafted CS degrades
faster than that of CS. The appearance of this stage
indicates the structure of CS chains has been changed
due to the grafting of NIPA chains.
3.2. Effects of monomer concentration and irradiation
dose
Fig. 3 gives the variation in grafting percentage
and grafting efciency with monomer concentration.
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160 140 120 100 80 60 40 20 0 -20
(b)
(a)
(c)
C1
C4
C3,5
C2,6
(d)
ppm
Fig. 1.
13
C-NMR spectra of (a) CS and (b) CS-g-NIPA.
0 200 400 600 800
20
40
60
80
100
(b)
(a)
T
G
%
Temperature (C)
Fig. 2. TGA curves of (a) CS and (b) CS-g-NIPA.
1:1 1:3 1:5 1:7
0
100
200
300
400
500
600
700
G
(
%
)

0
20
40
60
80
100
G
E
(
%
)
1:9
CS/NIPA (mol/mol)
Fig. 3. The effect of monomer concentration on the degree of
grafting and grafting efciency.
H. Cai et al. / Radiation Physics and Chemistry 74 (2005) 2630 28
Grafting was carried out at room temperature at a dose
of 10 kGy. The results showed that there is an increase in
the grafting percentage and grafting efciency with
increasing monomer concentration. During the grafting
process, the monomers continuously diffused into the
polymer. The ability of CS macroradicals to capture
NIPA depends on the availability of NIPA molecules in
their vicinity. Therefore, the increase in monomer
concentration leads to an increase in grafting percentage
and grafting efciency.
The effect of total irradiation dose on grafting
percentage and grafting efciency is presented in
Fig. 4. The graph exhibited an increase in grafting
percentage and grafting efciency with the increase in
the dose range from 3 to 10 kGy. The increase of
grafting percentage and grafting efciency may be due to
the increasing concentration of free radicals formed in
the polymer substrate.
3.3. Swelling studies
The effect of grafting percentage on the swelling ratios
for the hydrogels at room temperature is shown in
Fig. 5. It can be seen an increase in the swelling ratios
with the increase of grafting percentage. Clearly, the
swelling behavior of the hydrogels depends on the
amount of the grafted branches.
3.4. Thermal and pH analysis
The thermosensitivity of the hydrogels is shown in
Fig. 6, measured by the transparency of the hydrogels
under different temperature. There is a sharp decrease in
the transparency when the temperature is about 28 1C,
the LCST of the grafted hydrogels (620% grafting
percentage).
The swelling ratios for hydrogels in different pH
solutions shown in Fig. 7 indicate that the swelling ratios
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2 4 6 8 10
0
20
40
60
80
100
120
140
160
G
(
%
)
10
20
30
40
50
60
70
80
G
E
(
%
)
Irradiation Dose (KGy)
Fig. 4. The effect of irradiation dose on the degree of grafting
and grafting efciency.
100 200 300 400 500 600 700
4
6
8
10
12
14
16
18
20
22
S
w
e
l
l
i
n
g

r
a
t
i
o
Grafting Percentage(%)
Fig. 5. Swelling ratio as a function of grafting percentage.
20 25 30 35 40
0.03
0.04
0.05
0.06
0.07
0.08
0.09
0.10
T
%
t(C)
Fig. 6. Light transmission as a function of temperature
(l 500 nm).
0 2 4 6 8 10 12 14
0
5
10
15
20
25
S
w
e
l
l
i
n
g

r
a
t
i
o
pH
Fig. 7. Effect of pH on swelling ratios.
H. Cai et al. / Radiation Physics and Chemistry 74 (2005) 2630 29
decrease with the increase of pH value of the buffer
solutions. This is because PNIPA gels do not have pH
sensitivity in the buffer solution but CS has.
4. Conclusion
NIPA was successfully grafted onto CS by g-radiation
induced technology for the rst time. The grafting
percentage and grafting efciency can be controlled by
appropriate selection of grafting conditions, such as
monomer concentration and total irradiation dose. The
CS-g-NIPA hydrogels showed good thermo- and pH-
sensitivity and swelling property.
Acknowledgments
The authors are grateful to the CRC program of
Canada Mr. Yangeng Zhang of the Tianjin Institute of
Technological Physics for providing the radiation source
and helpful advice.
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