Thermosensitive chitosan hydrogel for biomaterial applications

1. Thermosensitive chitosan hydrogel for biomaterial applications Rong Zeng Queen Mary, University of London Fudan University Supervisor : Dr. Ray Smith Xin Chen

2. Contents • Background • Chitosan • Thermosensitive hydrogel • Experiments & Some results • GP/chitosan • thermosensitive chitosan hydrogel • Future work

3. Chitosan • Structure Biocompatibility Biodegradable Bioadhesive

4. Chitosan Hydrogel Temporary network Safe & reversible Weak mechanical properties Permanent network Stable &good mechanical properties Toxic

5. Temperature induced gelation Body temperature Injectable Topical drug delivery Tissue engineering Thermosensitive hydrogel

6. GP&chitosan Chenite et al.(2000) developed a novel approach to produce thermally sensitive neutral solutions based on chitosan /β-glycerophosphate (GP) combinations.

7. Three types of interactions may be involved in 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.

8. NMR test result • 1H-NMR • 13C-NMR • 31P-NMR

9. 1H-NMR 3,4,6 5,6

10. The line shifting is an indication of an exchange process which is speed up by increasing the temperature.

11. T increase

13. T increase

14. 13C-NMR 1,4,5,3,6,2

16. 31P-NMR

18. Gp/cs

19. Results • 1H NMR data on GP/Chitosan mixture indicates that 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.

20. Thermosensitive chitosan hydrogel PKa Method: 1, alkaline chitosan solution 2, change the PH value of the solution by using different kind of acid solution

22. alkaline chitosan solution (PH=9.6) pluronic solution (PH=4.4) . Mixed solution (PH=7.0)

23. T=37-38℃

24. Future work

25. Thank you !