Document Detail


The delivery of superoxide dismutase encapsulated in polyketal microparticles to rat myocardium and protection from myocardial ischemia-reperfusion injury.
MedLine Citation:
PMID:  19889454     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Oxidative stress is increased in the myocardium following infarction and plays a significant role in death of cardiac myocytes, leading to cardiac dysfunction. Levels of the endogenous antioxidant Cu/Zn-superoxide dismutase (SOD1) decrease following myocardial infarction. While SOD1 gene therapy studies show promise, trials with SOD1 protein have had little success due to poor pharmacokinetics and thus new delivery vehicles are needed. In this work, polyketal particles, a recently developed delivery vehicle, were used to make SOD1-encapsulated-microparticles (PKSOD). Our studies with cultured macrophages demonstrated that PKSOD treatment scavenges both intracellular and extracellular superoxide, suggesting efficient delivery of SOD1 protein to the inside of cells. In a rat model of ischemia/reperfusion (IR) injury, injection of PKSOD, and not free SOD1 or empty particles was able to scavenge IR-induced excess superoxide 3 days following infarction. In addition, only PKSOD treatment significantly reduced myocyte apoptosis. Further, PKSOD treatment was able to improve cardiac function as measured by acute changes in fractional shortening from baseline echocardiography, suggesting that sustained delivery of SOD1 is critical during the early phase of cardiac repair. These data demonstrate that delivery of SOD1 with polyketals is superior to free SOD1 protein therapy and may have potential clinical implications.
Authors:
Gokulakrishnan Seshadri; Jay C Sy; Milton Brown; Sergey Dikalov; Stephen C Yang; Niren Murthy; Michael E Davis
Related Documents :
7677534 - Ischemia affects cardiac proteins in healthy animals less severely than in human patients.
17710174 - Descriptive epidemiology of collegiate men's lacrosse injuries: national collegiate ath...
3770934 - Problems caused by the unstable thoracic wall and by cardiac injury due to blunt injury.
12707244 - Imbalance between tissue inhibitor of metalloproteinase-4 and matrix metalloproteinases...
8509814 - Diagnosing and treating ventricular tachycardia.
22617504 - Is it worth placing ventricular pacing wires in all patients post-coronary artery bypas...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2009-11-03
Journal Detail:
Title:  Biomaterials     Volume:  31     ISSN:  1878-5905     ISO Abbreviation:  Biomaterials     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-01-29     Completed Date:  2010-03-03     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  8100316     Medline TA:  Biomaterials     Country:  England    
Other Details:
Languages:  eng     Pagination:  1372-9     Citation Subset:  IM    
Copyright Information:
(c) 2009 Elsevier Ltd. All rights reserved.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Drug Carriers / chemistry*
Drug Compounding / methods*
Free Radical Scavengers / administration & dosage,  chemistry
Microspheres
Myocardial Reperfusion Injury / diagnosis,  prevention & control*
Rats
Rats, Sprague-Dawley
Superoxide Dismutase / administration & dosage*,  chemistry*
Treatment Outcome
Grant Support
ID/Acronym/Agency:
EB006418/EB/NIBIB NIH HHS; HL089120/HL/NHLBI NIH HHS; HL090601/HL/NHLBI NIH HHS; R01 HL090601/HL/NHLBI NIH HHS; R01 HL090601-01A2/HL/NHLBI NIH HHS; R21 HL089120/HL/NHLBI NIH HHS; R21 HL089120-01A1/HL/NHLBI NIH HHS; UO1 HL80711-01/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Drug Carriers; 0/Free Radical Scavengers; EC 1.15.1.1/Superoxide Dismutase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Nanoparticles functionalised with recombinant single chain Fv antibody fragments (scFv) for the magn...
Next Document:  Engineering a scaffold-free 3D tumor model for in vitro drug penetration studies.