Effective loading and controlled release of camptothecin by O- carboxymethylchitosan aggregates

1. Effective loading and controlled release of camptothecin by O-carboxymethylchitosanaggregates Liu Nan 4th semester in Ph. D course Lab. of Biopolymer Engineering 2007.5. 23

2. Introduction Object Experiment Results and discussion Conclusion Contents

3. Introduction

4. Introduction

5. Introduction

6. Introduction CH2OH CH2OCH2COOH O O H H O O OH H OH H H H H NH2 H NH2 n n Chitosan OCMCS

7. Introduction

8. Investigate the drug-loading as well as the controlled release behavior of OCMCS aggregates on CPT. • Discuss the release kinetic of CPT from aggregates. Object

9. Experiment

10. Materials Experiment

11. Synthesis of OCMCS Monochloroacetic acid 5g dissolved in isopropanol 25ml 2g chitosan immersed in 25ml 50% NaOH solution for 24h Experiment Reaction for 8h at room temperature.

12. Loading capacity of OCMCS aggregates Experiment

13. In vitro release study Experiment

14. In vitro cancer cell activity Experiment

15. MTS/PMS Assay • MTS is an analog of MTT • It has the similar reaction mechanism with MTT. • MTS to MTS-formazan. • The number of viable cells is correlated to the quantity of the formazan produced. Experiment

16. Results and discussion

17. Drug loading in OCMCS aggregates Results and discussion Fig. 1. Effect of OCMCS concentration on the fluorescence emission spectra of camptothecin in aqueous solution of OCMCS.

18. Drug loaded in OCMCS aggregates Results and discussion Fig. 2. CPT loading as a function of OCMCS concentrations.

19. Drug loaded in OCMCS aggregates The critical aggregation concentration (cac) of OCMCS is determined to be 0.05mg/ml. (Zhu et al., 2005) Results and discussion Fig. 3. CPT loading as a function of OCMCS concentrations.

20. The release of CPT from OCMCS aggregates t50%:the time 50% amount of the drug was released; teq : time to achieve equilibrium; Feq: the fraction of CPT released at equilibrium. Results and discussion Fig. 4. Release behavior of CPT from OCMCS in PBS (pH 7.4, 0.01M) solution at 37℃

21. Diffusion coefficients Diffusion coefficients Results and discussion Mt and M∞ are the absolute cumulative amounts of drug released at time t and infinite time. l is the thickness of the flat sample D is the diffusion coefficient.

22. Antitumor activity Results and discussion Fig. 5. the relative anti proliferative activity of cancer cell dependence on the OCMCS concentration.

23. Conclusion

24. A novel, biocompatible OCMCS aggregates were developed into a controlled drug delivery system. • The amount of drug loaded in OCMCS is strongly dependent on its concentration. • Not only the aggregates but also unimer of OCMCS can effectively load the hydrophobic CPT. • The maximum amount of CPT loaded in OCMCS was found to be 6 times than that of camptothecin in water at a concentration of OCMCS of 0.0625mg/ml. • The diffusion coefficient of CPT in the presence of OCMCS exhibits low. • In vitro measurements confirm the slow release behavior of CPT from OCMCS. Conclusions

25. Thanks for your attention! Q & A