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Novel strategies for cardiac drug de...

Sy, Jay Christopher.

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Novel strategies for cardiac drug delivery.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Novel strategies for cardiac drug delivery./
Author:	Sy, Jay Christopher.
Description:	144 p.
Notes:	Source: Dissertation Abstracts International, Volume: 72-10, Section: B, page: .
Contained By:	Dissertation Abstracts International72-10B.
Subject:	Chemistry, Pharmaceutical. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3464120
ISBN:	9781124759852

Novel strategies for cardiac drug delivery.
Sy, Jay Christopher.

Novel strategies for cardiac drug delivery. - 144 p.

Source: Dissertation Abstracts International, Volume: 72-10, Section: B, page: .

Thesis (Ph.D.)--Georgia Institute of Technology, 2011.

The American Heart Association (AHA) estimates that at least one American will die from a coronary event every minute, costing over

ISBN: 9781124759852Subjects--Topical Terms:

550957
Chemistry, Pharmaceutical.

Novel strategies for cardiac drug delivery.
LDR:04049nam 2200325 4500 001 1405781
005 20111214134959.5
008 130515s2011 ||||||||||||||||| ||eng d
020 $a 9781124759852
035 $a (UMI)AAI3464120
035 $a AAI3464120
040 $a UMI $c UMI
100 1 $a Sy, Jay Christopher. $3 1685193
245 1 0 $a Novel strategies for cardiac drug delivery.
300 $a 144 p.
500 $a Source: Dissertation Abstracts International, Volume: 72-10, Section: B, page: .
500 $a Adviser: Michal Davis.
502 $a Thesis (Ph.D.)--Georgia Institute of Technology, 2011.
520 $a The American Heart Association (AHA) estimates that at least one American will die from a coronary event every minute, costing over $1 50 billion in 2008 alone. Regenerating the myocardium of patients that survive the initial infarction has proven to be an elusive goal. A variety of factors -- including the loss of contractile cells, inflammatory response following infarction, cardiac hypertrophy, and lack of suitable cues for progenitor cells -- causes fibrosis in the heart and loss of cardiac function. This dissertation examines three drug delivery strategies aimed at improving conditions for cardiac regeneration: polyketal microspheres as non-inflammatory drug delivery vehicles; surface functionalization of microparticles with nitrilotriacetic acid-nickel (NTA-Ni) for non-covalent tethering of proteins; and using Hoechst-inspired ligands for targeting extracellular DNA in necrotic tissue.
520 $a The non-acidic degradation products of poly(cyclohexane-1,4-diyl acetone dimethylene ketal) (PCADK) make it a prime candidate for treating inflammatory disease. We tested the in vitro and in vitro biocompatibility of the polymer and found that it did not significantly recruit or activate inflammatory cells and had comparable proinflammatory cytokine levels compared to saline injection. We formulated microparticles containing SB239063, a p38 mitogen associated protein kinase (MAPK) inhibitor, and found that we were able to improve cardiac function in a rat model of myocardial infarction with PCADK microparticles, but not with size- and loadingmatched poly(lactic-co-glycolic acid) (PLGA) microparticles suggesting that the polymer chemistry played a role in preventing fibrosis.
520 $a NTA-Ni complexes are traditionally used in immobilized metal affinity chromatography (IMAC) purification of Histidine-tagged recombinant proteins. The surface of polymer microparticles was functionalized with NTA-Ni complexes, which can be used as a non-covalent tethering mechanism for therapeutic proteins and targeting ligands. Utilizing immobilized metal chelates prevents protein denaturation by eliminating exposure of proteins to organic solvent and maintains high loading efficiency, even when using dilute protein solutions. Bioactive growth factors can be released from the microparticles and modest cell surface targeting was achieved using vascular endothelial growth factor (VEGF) and vascular-endothelial cadherin (VE-Cadherin) as model protein systems.
520 $a Traditional drug targeting schemes rely on antibody-antigen interactions. This strategy inherently limits the lower bound of the size, and therefore diffusivity, of a drug delivery vehicle. Furthermore, this strategy relies on identifying protein antigens with tissue-specific expression or upregulation. Instead, studies focused on examining the potential for targeting another biomarker for tissue damage post-myocardial infarction, extracellular deoxyribonucleic acid (DNA) generated in necrotic cell death. Using Hoechst as an inspiration, a variety of conjugates were synthesized that can be used for protein delivery and imaging necrotic tissue after infarction.
590 $a School code: 0078.
650 4 $a Chemistry, Pharmaceutical. $3 550957
650 4 $a Engineering, Biomedical. $3 1017684
650 4 $a Health Sciences, Pharmacy. $3 1017737
690 $a 0491
690 $a 0541
690 $a 0572
710 2 $a Georgia Institute of Technology. $3 696730
773 0 $t Dissertation Abstracts International $g 72-10B.
790 1 0 $a Davis, Michal, $e advisor
790 $a 0078
791 $a Ph.D.
792 $a 2011
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3464120