Transcript Document

Thermosensitive chitosan hydrogel
for biomaterial applications
Rong Zeng
Queen Mary, University of London
Fudan University
Supervisor : Dr. Ray Smith
Xin Chen
Contents
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Background
Chitosan
Thermosensitive hydrogel
Experiments & Some results
GP/chitosan
thermosensitive chitosan hydrogel
Future work
Chitosan
• Structure
Biocompatibility
Biodegradable
Bioadhesive
Chitosan Hydrogel
Chitosan Hydrogel
chemical
Covalent bonds
physical
electrostatic attraction
Hydrogen bonds
Permanent network
Temporary network
Stable &good mechanical
properties
Safe & reversible
Toxic
Hydrophobic interaction
Weak mechanical properties
Thermosensitive hydrogel
• Temperature
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induced gelation
Body temperature
Injectable
Topical drug delivery
Tissue engineering
GP&chitosan
Chenite et al.(2000) developed a novel
approach to produce thermally sensitive
neutral solutions based on chitosan /βglycerophosphate (GP) combinations.
• Three types of interactions may be involved in
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the gelation process:
(1) electrostatic attraction between the
ammonium groups of chitosan and the
phosphate group of GP;
(2) hydrogen bonding between polymer chains
as a consequence of reduced electrostatic
repulsion after neutralization of the chitosan
solution with GP;
(3) chitosan–chitosan hydrophobic interactions.
NMR test result
• 1H-NMR
• 13C-NMR
• 31P-NMR
1H-NMR
3,4,6 5,6
The line shifting is an indication of an exchange process which is speed
up by increasing the temperature.
T increase
3.4
3.6
3.8
chemical shift
4.0
4.2
Temperatu
re
Chemical
shift
297k
299k
301k
303k
305k
307k
309k
311k
313k
315k
317k
3.584
3.604
3.623
3.643
3.661
3.681
3.700
3.719
3.739
3.758
3.776
difference
0.020
0.019
0.020
0.018
0.020
0.019
0.019
0.020
0.019
0.018
T increase
5.9
6.0
6.1
chemical shift
6.2
6.3
6.0720
6.0886
6.1057
6.1227
6.1384
6.1551
6.1715
6.1878
6.2039
6.2200
6.2361
297k
299
301
303
305
307
309
311
313
315
317
0.0166
0.0171
0.0170
0.0157
0.0167
0.0164
0.0163
0.0161
0.0161
0.0161
13C-NMR
1,4,5,3,6,2
31P-NMR
temperature
Chemical shfit
intensity
Difference
of
shift
50
7.1509
535826190
45
7.0696
304493054
0.0813
40
6.9836
343689033
0.0860
35
6.9000
390762637
0.0836
30
6.8184
455897133
0.0816
25
6.7259
447827372
0.0825
6.4
6.6
6.8
7.0
chemical shift
7.2
7.4
7.6
5.7
5.8
5.9
6.0
6.1
6.2
chemical
shift
Gp/cs
6.3
6.4
6.5
6.6
temperature
Chemical shfit
intensity
Difference
of shift
25
5.9115
370514336
0.0281
30
5.9396
364484186
0.0263
35
5.9659
349408809
0.0198
40
5.9857
319258055
0.0082
45
5.9939
286269583
0.0018
50
5.9957
501226722
Results
• 1H NMR data on GP/Chitosan mixture indicates that
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hydrogen bonds have been disrupted as a result of
increasing temperature. If GP alone is heated, the
observed shifts are much smaller.
13C NMR data was difficult to obtain for chitosan
solutions, still trying to investigate the affect of
temperature . But we expect no major shift.
31P data again indicate that in mixture of GP/ Chitosan
the hydrogen bonds have been disrupted. This is shown
in a difference in shift value between GP and
GP/Chitosan . We are closely examining the 31P-1H
coupled data to verify this.
Thermosensitive chitosan hydrogel
PKa
Method:
1, alkaline chitosan solution
2, change the PH value of the solution by using
different kind of acid solution
alkaline
chitosan
4.0
3.5
3.0
absorption
2.5
2.0
1.5
1.0
0.5
0.0
0
500
1000
1500
2000
2500
3000
-1
wave number(cm )
3500
4000
4500
.
alkaline chitosan solution
(PH=9.6)
pluronic solution (PH=4.4)
Mixed solution
(PH=7.0)
T=3738℃
Future work
Thank you !