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Synthesis of Biodegradable Nanospheres for Side-Effect-Free Anti-Cancer Drug Delivery (2007). Nicholas Derrico. Background. Cancer causes 13% of all deaths worldwide. Background. Cancer causes 13% of all deaths worldwide Cancer has no cure. Background. - PowerPoint PPT Presentation
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Synthesis of Biodegradable Nanospheres forSide-Effect-Free Anti-Cancer Drug Delivery
(2007)
Nicholas Derrico
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BackgroundBackground
• Cancer causes 13% of all deaths worldwide
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BackgroundBackground
• Cancer causes 13% of all deaths worldwide• Cancer has no cure
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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.
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Purpose
• To develop a cutting-edge, side-effect-free delivery system to encapsulate camptothecin in biodegradable, biocompatible nanospheres that will target only cancer cells
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Background
• Cancer cells have leaky vasculature
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Background
• Cancer cells have leaky vasculature
<200 nm
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Previous Studies
• Sheihet (2007) successfully encapsulated the drug paclitaxel
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Previous Studies
• Sheihet (2007) successfully encapsulated the drug paclitaxel
• Gounder (2007) used biodegradable, biocompatible nanospheres to kill cancer in mice without side-effects
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Goals
• To synthesize nanospheres from ABA-triblock copolymers that are < 200 nm in hydrodynamic diameter
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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
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ABA-Triblock Copolymer
• Biodegradable
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ABA Triblock Copolymer
• Biodegradable
• Biocompatible
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ABA Triblock Copolymer
• Biodegradable
• Biocompatible
• Non-cytotoxic
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ABA Triblock Copolymer
• Biodegradable
• Biocompatible
• Non-cytotoxic
• Spontaneously self-assemble into nanospheres in aqueous solution
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B-Block
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Desaminotyrosyl Tyrosine Alkyl Ester
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Desaminotyrosyl Tyrosine Alkyl Ester
R = Pendant Chains
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Desaminotyrosyl Tyrosine Butyl Ester
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Desaminotyrosyl Tyrosine Octyl Ester
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Desaminotyrosyl Tyrosine Dodecyl Ester
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Desaminotyrosyl Tyrosine Benzyl Ester
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Desaminotyrosyl Tyrosine Alkyl Ester
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Suberic Acid
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B-Block
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Poly(ethylene glycol) = A-Block
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Self-Assembling into Nanospheres
B-Block
A-Block
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Self-Assembling into Nanospheres
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Self-Assembling into Nanospheres
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Self-Assembling into Nanospheres
=
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Self-Assembling into Nanospheres
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Self-Assembling into Nanospheres
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Self-Assembling into Nanospheres
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Self-Assembling into Nanospheres
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Self-Assembling into Nanospheres
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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%
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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%
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Camptothecin Only Nanospheres
Results
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Camptothecin Only Nanospheres
Results
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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
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-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
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Conclusion
• 15% camptothecin was encapsulated
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Conclusion
• 15% camptothecin was encapsulated
• Pelleting occurred during ultracentrifugation
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Future Study
• Use ultrafiltration in procedure
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Acknowledgements
• Team Research
• Larisa Sheihet Ph.D
• Will Mallon
• Ms. Lois Fruen
QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.
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Questions?
Synthesis of Biodegradable Nanospheres forSide-Effect-Free Anti-Cancer Drug Delivery
(2007)
Nicholas Derrico