1. Synthesis of Biodegradable Nanospheres for Side-Effect-Free Anti-Cancer Drug Delivery (2007) Nicholas Derrico

2. 1 Background Cancer causes 13% of all deaths worldwide

3. 2 Background Cancer has no cure

4. 3 Background Cancer causes 13% of all deaths worldwide Cancer has no cure-all Chemotherapy dissolves highly toxic drugs into hydrophobic solutions, which are then administered to the patient, killing cells indiscriminately.

5. 4 Purpose To develop a cutting-edge, side-effect-free delivery system to encapsulate camptothecin in biodegradable, biocompatible nanospheres that will target only cancer cells

6. 5 Background Cancer cells have leaky vasculature

7. 6 Background Cancer cells have leaky vasculature <200 nm

8. 7 Previous Studies Sheihet (2007) successfully encapsulated the drug paclitaxel

9. 8 Previous Studies Sheihet (2007) successfully encapsulated the drug paclitaxel Gounder (2007) used biodegradable, biocompatible nanospheres to kill cancer in mice without side-effects

10. 9 Goals To synthesize nanospheres from ABA- triblock copolymers that are < 200 nm in hydrodynamic diameter

11. 10 Goals To synthesize nanospheres from ABA- triblock copolymers that are < 200 nm in hydrodynamic diameter To determine the composition of ABA- triblock copolymers that will form nanospheres that can hold as much camptothecin as possible

12. 11 ABA-Triblock Copolymer Biodegradable

13. 12 ABA Triblock Copolymer Biodegradable Biocompatible

14. 13 ABA Triblock Copolymer Biodegradable Biocompatible Non-cytotoxic

15. 14 ABA Triblock Copolymer Biodegradable Biocompatible Non-cytotoxic Spontaneously self-assemble into nanospheres in aqueous solution

16. 15 B-Block

17. 16 Desaminotyrosyl Tyrosine Alkyl Ester

18. 17 Desaminotyrosyl Tyrosine Alkyl Ester R = Pendant Chains

19. 18 Desaminotyrosyl Tyrosine Butyl Ester

20. 19 Desaminotyrosyl Tyrosine Octyl Ester

21. 20 Desaminotyrosyl Tyrosine Dodecyl Ester

22. 21 Desaminotyrosyl Tyrosine Benzyl Ester

23. 22 Desaminotyrosyl Tyrosine Alkyl Ester

24. 23 Suberic Acid

25. 24 B-Block

26. 25 Poly(ethylene glycol) = A-Block

27. 26 Self-Assembling into Nanospheres B-Block A-Block

28. 27 Self-Assembling into Nanospheres

29. 28 Self-Assembling into Nanospheres

30. 29 Self-Assembling into Nanospheres =

31. 30 Self-Assembling into Nanospheres

32. 31 Self-Assembling into Nanospheres

33. 32 Self-Assembling into Nanospheres

34. 33 Self-Assembling into Nanospheres

35. 34

36. 35 Self-Assembling into Nanospheres

37. 36 Compositions CopolymersRatios DTB-SA/5K100% DTO-SA/5K100% DTD-SA/5K100% DTBn-SA/5K100% DTB-SA/5K + DTO-SA/5K50%-50% DTB-SA/5K + DTD-SA/5K50%-50% DTB-SA/5K + DTBn-SA/5K50%-50% DTB-SA/5K + DTO-SA/5K DTD-SA/5K + DTBn-SA/5K 25%-25%

38. 37 Compositions CopolymersRatios DTB-SA/5K100% DTO-SA/5K100% DTD-SA/5K100% DTBn-SA/5K100% DTB-SA/5K + DTO-SA/5K50%-50% DTB-SA/5K + DTD-SA/5K50%-50% DTB-SA/5K + DTBn-SA/5K50%-50% DTB-SA/5K + DTO-SA/5K DTD-SA/5K + DTBn-SA/5K 25%-25%

39. 38 Camptothecin Only Nanospheres Results

40. 39 Camptothecin Only Nanospheres Results

41. 40 Figure 5: VD3 Binding Efficiency of 3 best copolymer compositions Binding Efficiencies of Vitamin D3

42. 41 Figure 4: CPT Binding Efficiency of 3 best copolymer compositions Binding Efficiencies of Camptothecin

43. 42 Conclusion 15% camptothecin was encapsulated

44. 43 Conclusion 15% camptothecin was encapsulated Pelleting occurred during ultracentrifugation

45. 44 Future Study Use ultrafiltration in procedure

46. 45 Acknowledgements Team Research Larisa Sheihet Ph.D Will Mallon Ms. Lois Fruen

47. 46 Questions?

48. Synthesis of Biodegradable Nanospheres for Side-Effect-Free Anti-Cancer Drug Delivery (2007) Nicholas Derrico