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

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Presentation transcript:

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

1 Background Cancer causes 13% of all deaths worldwide

2 Background Cancer has no cure

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.

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

5 Background Cancer cells have leaky vasculature

6 Background Cancer cells have leaky vasculature <200 nm

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

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

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

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

11 ABA-Triblock Copolymer Biodegradable

12 ABA Triblock Copolymer Biodegradable Biocompatible

13 ABA Triblock Copolymer Biodegradable Biocompatible Non-cytotoxic

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

15 B-Block

16 Desaminotyrosyl Tyrosine Alkyl Ester

17 Desaminotyrosyl Tyrosine Alkyl Ester R = Pendant Chains

18 Desaminotyrosyl Tyrosine Butyl Ester

19 Desaminotyrosyl Tyrosine Octyl Ester

20 Desaminotyrosyl Tyrosine Dodecyl Ester

21 Desaminotyrosyl Tyrosine Benzyl Ester

22 Desaminotyrosyl Tyrosine Alkyl Ester

23 Suberic Acid

24 B-Block

25 Poly(ethylene glycol) = A-Block

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

27 Self-Assembling into Nanospheres

28 Self-Assembling into Nanospheres

29 Self-Assembling into Nanospheres =

30 Self-Assembling into Nanospheres

31 Self-Assembling into Nanospheres

32 Self-Assembling into Nanospheres

33 Self-Assembling into Nanospheres

34

35 Self-Assembling into Nanospheres

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%

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%

38 Camptothecin Only Nanospheres Results

39 Camptothecin Only Nanospheres Results

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

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

42 Conclusion 15% camptothecin was encapsulated

43 Conclusion 15% camptothecin was encapsulated Pelleting occurred during ultracentrifugation

44 Future Study Use ultrafiltration in procedure

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

46 Questions?

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