Deglau, Timothy Edward
(2005)
Surface Modified Vascular Tissue for Targeted Delivery.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Thrombosis and restenosis are common problems associated with intravascular procedures such as anastomoses, balloon angioplasty, and carotid endarterectomies. Application of a molecular barrier at the site of injury to inhibit platelet deposition would be advantageous. Additional therapeutic benefit could be achieved if the modified surface provided a target for delivery of pharmaceuticals, vectors, or cells. This dissertation focuses on the development of an intravascular modification and targeted delivery system that possesses numerous potential applications in the treatment of vascular injury.Polyethylene glycol is commonly used for modification of molecules and surfaces to increase biocompatibility, reduce immunogenicity, and provide stealth characteristics. Protein-reactive polyethylene glycols could be used to modify vascular surfaces forming a molecular barrier. In addition, the polymer could be used as a target for delivery of agents by applying a recognizable tag to the terminus. Agents could be targeted to modified vascular tissue using, for instance, the biotin/avidin recognition system.The ability to modify vascular surfaces with protein-reactive polyethylene glycols was confirmed using quantitative flow cytometry and epi-fluorescence microscopy. Furthermore, in vitro perfusion studies with cultured cells and scrape-damaged arteries demonstrated preferential delivery of microspheres and cells to polyethylene glycol-biotin modified vascular surfaces.An in vivo rabbit model provided a more rigorous assessment of the polymer modification and targeted delivery system. Polymer modification of balloon injured rabbit femoral arteries persisted for a minimum of 72 hours. Targeted microspheres preferentially adhered to healthy and injured arteries modified with the reactive polymer as opposed to untreated controls. Furthermore, the ability to target microspheres to the modified arteries persisted for a minimum of 72 hours.In conclusion, it was shown that it is possible to modify vascular tissue with a protein-reactive polyethylene glycol and that this modification with signaling molecules can also provide a target for the site-specific delivery of vascular-infused agents. An intravascular targeted delivery system such as this might find numerous applications in the treatment of intravascular injury that is associated with angioplasty, stenting, and endarterectomy procedures.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Deglau, Timothy Edward | tedst9@pitt.edu | TEDST9 | |
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| ETD Committee: |
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| Date: |
13 October 2005 |
| Date Type: |
Completion |
| Defense Date: |
5 July 2005 |
| Approval Date: |
13 October 2005 |
| Submission Date: |
25 July 2005 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Swanson School of Engineering > Bioengineering |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
angioplasty; endothelial cells; intravascular; microspheres; polyethylene glycol; targeted delivery |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-07252005-130509/, etd-07252005-130509 |
| Date Deposited: |
10 Nov 2011 19:53 |
| Last Modified: |
19 Dec 2016 14:36 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/8582 |
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