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EFFECT OF SHEAR FORCES ON
NANOCRYSTAL DRUG CARRIERS
Megan Castiel, Celeste Parra, Ekta Shahani, Youssef Sibih
Project Mentor: Izzy Jarvis
PI: Dr. Samir Mitragotri
1
Targeted Cancer Therapy Reduces Side Effects
Nonspecific therapy Targeted therapy
Images courtesy of designandviolence.moma.org
2
Folic Acid Delivers Drug to Cancerous Cells
Polymer (“linker”)
Small Molecule/Folic Acid
Drug (crystallized Camptothecin)
3
(-)
Polymers Shed off Due to Weak Interaction
4
Complex vessel system model
(microvasculature)
Simple vessel system model
(straight channel)
Microfluidic Systems Simulate Architecture of
Drug Delivery Path
5
Mimicking In Vivo Conditions through Microfluidics
channel coating
crystal
3µm
6
0.02 µm
Microvascular Devices Show
Consistent Shearing
7
CountofNanocrystals(104)
Apparent Zeta Potential (mV)
Initial Particles vs. Flowed Particles
20
-100 0
40
60
80
Stock
Sample
- charge + charge
8
Apparent Zeta Potential (mV)
Straight Channel Devices Show
Variance in Shearing
Initial Particles vs. Flowed Particles
20
40
60
80
-100 0
Stock
Sample
CountofNanocrystals(104)
?
?
?
- charge + charge
9
Amount of Folic Acid (mg)
Amount of Folic Acid Remaining
0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9
Quantitative Data Shows Shear Forces in All Devices
Complex A
Complex B
Straight A
Straight B
Straight C
Stock
10
Selecting a Small Molecule that
Resists Extraneous Attractions
Acknowledgements
■ Izzy Jarvis and Dr. Samir Mitragotri
■ Supermentors: Dr. Stephanie Mendes
and Dean Morales
■ SIMS Coordinator: Mary Alice Callaghan
■ Resident Advisors: Rachel Alvelais,
Stephen Chih, Marine Minasyan, and
Joseph Sanz
11

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BMSE_Final

  • 1. EFFECT OF SHEAR FORCES ON NANOCRYSTAL DRUG CARRIERS Megan Castiel, Celeste Parra, Ekta Shahani, Youssef Sibih Project Mentor: Izzy Jarvis PI: Dr. Samir Mitragotri 1
  • 2. Targeted Cancer Therapy Reduces Side Effects Nonspecific therapy Targeted therapy Images courtesy of designandviolence.moma.org 2
  • 3. Folic Acid Delivers Drug to Cancerous Cells Polymer (“linker”) Small Molecule/Folic Acid Drug (crystallized Camptothecin) 3 (-)
  • 4. Polymers Shed off Due to Weak Interaction 4
  • 5. Complex vessel system model (microvasculature) Simple vessel system model (straight channel) Microfluidic Systems Simulate Architecture of Drug Delivery Path 5
  • 6. Mimicking In Vivo Conditions through Microfluidics channel coating crystal 3µm 6 0.02 µm
  • 7. Microvascular Devices Show Consistent Shearing 7 CountofNanocrystals(104) Apparent Zeta Potential (mV) Initial Particles vs. Flowed Particles 20 -100 0 40 60 80 Stock Sample - charge + charge
  • 8. 8 Apparent Zeta Potential (mV) Straight Channel Devices Show Variance in Shearing Initial Particles vs. Flowed Particles 20 40 60 80 -100 0 Stock Sample CountofNanocrystals(104) ? ? ? - charge + charge
  • 9. 9 Amount of Folic Acid (mg) Amount of Folic Acid Remaining 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 Quantitative Data Shows Shear Forces in All Devices Complex A Complex B Straight A Straight B Straight C Stock
  • 10. 10 Selecting a Small Molecule that Resists Extraneous Attractions
  • 11. Acknowledgements ■ Izzy Jarvis and Dr. Samir Mitragotri ■ Supermentors: Dr. Stephanie Mendes and Dean Morales ■ SIMS Coordinator: Mary Alice Callaghan ■ Resident Advisors: Rachel Alvelais, Stephen Chih, Marine Minasyan, and Joseph Sanz 11

Editor's Notes

  1. Megan: -current cancer therapies work by introducing toxins to cells -healthy cells are harmed in the process -targeted therapy is seeking out only cancerous cells -explain analogy
  2. Ekta: -introduce 3 parts of drug **crystal itself is made of the drug, current methods are mostly attaching the drug to another compound/particle -camptothecin is a drug that prevents breast cancer cells from reproducing -polymer serves 2 purposes: 1) allows crystal to travel through the body w/out being detected by immune system 2) links folic acid to carrier -Breast cancer cells, cell takes in drug preventing replication have folic acid receptors, folic acid takes carrier to those cells -scaffold can be modified
  3. Celeste
  4. Youssef Sibih:  -flowing carriers through microfluidic devices -> describe different devices -have found that shearing forces rip polymers off of carrier -> problematic bc polymers are linkers and carriers need them to travel -hypothesis: architecture does NOT effect amount of polymer that falls off, only due to shearing force -goal: send carriers through both, quantitatively compare amount of polymer that comes off
  5. Celeste: **ask what absorbance/fluorescence device is called Attached tubes to flow carriers through Coated tubes to mimic the extracellular matrix inside veins Incubated devices to match vein temperature Used standard curve/absorbance/fluorescence to determine drug concentration because we wanted to dilute to 100 mg/mL The pump shown pushes the fluid through the devices at 4 mL/min
  6. Ekta
  7. Youssef Sibih
  8. Celeste