Sivak, Wesley N
(2007)
Synthesis and Characterization of Novel Polyurethane Drug Delivery Systems.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Selective delivery of drugs to localized regions of tissue within the body is a complex problem, representing one path through which the efficacy of many pharmaceutical compounds can be enhanced. Many pharmaceutical compounds show excellent activity in vitro, but their uses are severely limited in vivo. Unstable active conformations, limited membrane diffusion, rapid metabolism and/or clearance, decreased solubility, and dose-limiting systemic toxicity are just a few areas in which potential problems exist, halting drug development. Compounds exist possessing ideal pharmacologic activity for treating specific disease states, but they are simply unable to be delivered in adequate quantities or in the proper active conformation to the target site in the body. The following dissertation details the synthesis, characterization, and performance of a series of polyurethane drug delivery systems based on amino acids and the simple carbohydrates. The materials were synthesized from lysine diisocyanate (LDI) and glycerol with the aid of various tertiary amine and organometallic urethane catalysts. Candidate drugs were incorporated into the materials by way of labile urethane and urea linkages; subsequent drug release relied on the passive hydrolysis of the tethering bonds. Drug release from the materials correlated to material morphology, urethane catalyst, and chemical functionality of the incorporated drug. A single-phase polyurethane material was designed, synthesized, and shown capable of simultaneously releasing multiple pharmacologic agents at different rates. Finally, naturally occurring ionic ligands were incorporated into the LDI-glycerol polyurethanes to alter their swelling characteristics and release kinetics. This endeavor has resulted in the formulation of a series of polyurethane materials, capable of long-term controlled release of pharmacologic agents within the body. The structure-function relationships elucidated provide key design criteria, which can ultimately be used to develop such advanced degradable polyurethane materials.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
25 September 2007 |
| Date Type: |
Completion |
| Defense Date: |
6 July 2007 |
| Approval Date: |
25 September 2007 |
| Submission Date: |
16 July 2007 |
| 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: |
anthracycline; anti-cancer; anti-tumor; biocompatible; biodegradable; camptothecin; glioma; implant; naphthalene; organometallic; taxane; urethane catalysis |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-07162007-170922/, etd-07162007-170922 |
| Date Deposited: |
10 Nov 2011 19:51 |
| Last Modified: |
19 Dec 2016 14:36 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/8401 |
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