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ASD Project

Lucas, Amrick, Hilary
by

Hilary Ngai

on 13 August 2014

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Transcript of ASD Project

Solution?
PDGF Delivery through Liposomes triggered by Ultrasound to regenerate the tissue surrounding the secundum ASD
Creating Our Liposomes
- Intercalating Polyethylene glycol (PEG) between layers of a bilipid film.
- Hydration causes said film to spread out.
- The PDGF is introduced in solution so that it will be enclosed inside the liposomes.
- Agitating the sample forms large multilamelar vesicles.
- High pressure homogenization is used to reduce the size of the vesicles and form SUVs.
Atrial Septal Defect background
Ultrasonic effect on Liposomes
- When the ultrasonic oscillations of the ultrasound probe contact the liposome they causes a bubble to form in the hydrophobic layer.
- The bubble the enlarges until it causes an opening in the layer, forming a pore through which the PDGF can diffuse.
- After, the bilayer returns to its initial sealed structure.
Entry Point
The femoral vein (FV) hosts the conditions ideal for the injection of the liposomes:
- It is easily accessible
- Standard entry point for many procedures

PDGF Induced Regeneration
via Liposome Ultrasonic Lysing
(PRLUL)

Platelet Derived Growth Factor (PDGF)
- A Growth Factor (GF) that acts as a mitogen for cells of mesenchymal origin (Circulatory, Lymphatic and Connective tissues).
- Receptor Tyrosine Kinase (RTK) is a cell surface receptor that is auto-phosphorylated by in the presence of PDGF.
- The cell skips the G1 checkpoints of mitosis.
Liposomes
- Liposomes are biodegradable, biologically inert and minimally toxic to the body.
- Surface modifications, (Polyethylene glycol) PEGylation, links PEG covalently to the surface of liposomes.
- A protective steric barrier prevents liposomes from being phagocytized, prevents fusion, and increases circulation time.
- These properties are ideal when the PEG:Phospholipid mole ratio is ~1.2:1 (
Malinin et al., 2002; Needham et al., 1997
).
- PEG in the liposome absorbs ultrasound, thereby concentrating ultrasonic energy at the bilayer surface.
Aim:
- come up with a non-invasive way to cure ostium secundum atrial septal defect
Problems arising
- oxygenated blood flows directly to mix with deoxygenated blood

- causing "shunt"

- lead to lower than normal oxygen levels in arterial blood
The Pathway
- The Liposomes will travel from the entry point to the heart through the IVC.
- The heart will pump the liposomes to the lungs and only when they return to the heart will they begin to have an effect.
- A small targeted ultrasound probe will be delivering oscillations to the site of the foramen ovale.
- The liposomes will split:
A group will be forced into the ASD
A group will continue down the LV
- Only the group in the ASD will be perforated by the ultrasound frequency and the release of PDGF is triggered.
Once the PDGF is out
- PDGF functions by binding the RTK.
- The growth of the cells in the area of the foramen ovale will be irregular and not perfectly concealed to the secundum foramen ovale.
- However, the overall growth of repeated dosages will manage to seal the ASD.
L..Cocco
A. Randhawa
H. Ngai

Sources
Schroeder, Avi, Joseph Kost, and Yechezkel Barenholz. "Ultrasound, Liposomes, and Drug Delivery: Principles for Using Ultrasound to Control the Release of Drugs from Liposomes." Chemistry and Physics of Lipids 162.1-2 (2009): 1-16. Web.

Netter's Clinical Anatomy by John T Hansen 3rd Edition El Sevier Sauders 2014

"MIT: Langer Lab." MIT: Langer Lab. N.p., n.d. Web. 13 Aug. 2014.
Zamani, Maedeh, Molamma P. Prabhakaran, and Seeram Ramakrishna. "Abstract." National Center for Biotechnology Information. U.S. National Library of Medicine, 09 Aug. 2013. Web. 13 Aug. 2014.
"Result Filters." National Center for Biotechnology Information. U.S. National Library of Medicine, n.d. Web. 13 Aug. 2014.
"Result Filters." National Center for Biotechnology Information. U.S. National Library of Medicine, n.d. Web. 13 Aug. 2014.
"University of Iowa College of Pharmacy." Drug Delivery & Tissue Engineering. N.p., n.d. Web. 13 Aug. 2014.
"Pulmonary Drug Delivery." Academia.edu. N.p., n.d. Web. 13 Aug. 2014.
Acknowledgments
We would like to thank everybody here at Stanford who helped us with our project, especially:
Paul A. Chang for constantly listening to our ideas and his input.
Bhagat Patlolla for his input.
Grace Xiong for her recommendations.
Our TAs, RAs and fellow interns for their constant inspiration.
Details
- Liposomes will be extracted from the serum of the same patient to minimize rejection and avoid xenografts
- The dosage of PDGF to be used will be determined by more research on animals; however, we proposed using 0.1 to 0.5 μg/kg
- Pigs host the most appropriate conditions for said research
- This method has side effect that are not well know yet, and should not be used if the patient suffers from any genetic predisposition for tumour formations
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