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

Synthesis of Biodegradable Nanospheres forSide-Effect-Free Anti-Cancer Drug Delivery

(2007)

Nicholas Derrico

2

BackgroundBackground

• Cancer causes 13% of all deaths worldwide

3

BackgroundBackground

• Cancer causes 13% of all deaths worldwide• Cancer has no cure

4

BackgroundBackground

• 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

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

Background

• Cancer cells have leaky vasculature

7

Background

• Cancer cells have leaky vasculature

<200 nm

8

Previous Studies

• Sheihet (2007) successfully encapsulated the drug paclitaxel

9

Previous Studies

• Sheihet (2007) successfully encapsulated the drug paclitaxel

• Gounder (2007) used biodegradable, biocompatible nanospheres to kill cancer in mice without side-effects

10

Goals

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

11

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

ABA-Triblock Copolymer

• Biodegradable

13

ABA Triblock Copolymer

• Biodegradable

• Biocompatible

14

ABA Triblock Copolymer

• Biodegradable

• Biocompatible

• Non-cytotoxic

15

ABA Triblock Copolymer

• Biodegradable

• Biocompatible

• Non-cytotoxic

• Spontaneously self-assemble into nanospheres in aqueous solution

16

B-Block

17

Desaminotyrosyl Tyrosine Alkyl Ester

18

Desaminotyrosyl Tyrosine Alkyl Ester

R = Pendant Chains

19

Desaminotyrosyl Tyrosine Butyl Ester

20

Desaminotyrosyl Tyrosine Octyl Ester

21

Desaminotyrosyl Tyrosine Dodecyl Ester

22

Desaminotyrosyl Tyrosine Benzyl Ester

23

Desaminotyrosyl Tyrosine Alkyl Ester

24

Suberic Acid

25

B-Block

26

Poly(ethylene glycol) = A-Block

27

Self-Assembling into Nanospheres

B-Block

A-Block

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

Self-Assembling into Nanospheres

35

36

Self-Assembling into Nanospheres

37

CompositionsCopolymers Ratios

DTB-SA/5K 100%

DTO-SA/5K 100%

DTD-SA/5K 100%

DTBn-SA/5K 100%

DTB-SA/5K + DTO-SA/5K 50%-50%

DTB-SA/5K + DTD-SA/5K 50%-50%

DTB-SA/5K + DTBn-SA/5K 50%-50%

DTB-SA/5K + DTO-SA/5K

DTD-SA/5K + DTBn-SA/5K

25%-25%

25%-25%

38

CompositionsCopolymers Ratios

DTB-SA/5K 100%

DTO-SA/5K 100%

DTD-SA/5K 100%

DTBn-SA/5K 100%

DTB-SA/5K + DTO-SA/5K 50%-50%

DTB-SA/5K + DTD-SA/5K 50%-50%

DTB-SA/5K + DTBn-SA/5K 50%-50%

DTB-SA/5K + DTO-SA/5K

DTD-SA/5K + DTBn-SA/5K

25%-25%

25%-25%

39

Camptothecin Only Nanospheres

Results

40

Camptothecin Only Nanospheres

Results

41

0

10

20

30

40

50

60

70

1 to 1 1 to 3 1 to 6

CPT:VD3 Ratio wt/wt

VD3 Binding Efficiency

DTB-SA/5K

DTBn-SA/5K(DTB+DTBn)-SA/5K

Figure 5: VD3 Binding Efficiency of 3 best copolymer compositionsBinding Efficiencies of

Vitamin D3

42

-8

-6

-4

-2

0

2

4

6

8

10

12

1 to 1 1 to 3 1 to 6

CPT:VD3 Ratio wt/wt

CPT Binding Efficiency

DTB-SA/5K

DTBn-SA/5K(DTB+DTBn)-SA/5K

Figure 4: CPT Binding Efficiency of 3 best copolymer compositionsBinding Efficiencies of

Camptothecin

43

Conclusion

• 15% camptothecin was encapsulated

44

Conclusion

• 15% camptothecin was encapsulated

• Pelleting occurred during ultracentrifugation

45

Future Study

• Use ultrafiltration in procedure

46

Acknowledgements

• Team Research

• Larisa Sheihet Ph.D

• Will Mallon

• Ms. Lois Fruen

QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.

47

Questions?

Synthesis of Biodegradable Nanospheres forSide-Effect-Free Anti-Cancer Drug Delivery

(2007)

Nicholas Derrico