Document Detail


Targeted delivery of therapeutics to endothelium.
MedLine Citation:
PMID:  18815813     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The endothelium is a target for therapeutic and diagnostic interventions in a plethora of human disease conditions including ischemia, inflammation, edema, oxidative stress, thrombosis and hemorrhage, and metabolic and oncological diseases. Unfortunately, drugs have no affinity to the endothelium, thereby limiting the localization, timing, specificity, safety, and effectiveness of therapeutic interventions. Molecular determinants on the surface of resting and pathologically altered endothelial cells, including cell adhesion molecules, peptidases, and receptors involved in endocytosis, can be used for drug delivery to the endothelial surface and into intracellular compartments. Drug delivery platforms such as protein conjugates, recombinant fusion constructs, targeted liposomes, and stealth polymer carriers have been designed to target drugs and imaging agents to these determinants. We review endothelial target determinants and drug delivery systems, describe parameters that control the binding of drug carriers to the endothelium, and provide examples of the endothelial targeting of therapeutic enzymes designed for the treatment of acute vascular disorders including ischemia, oxidative stress, inflammation, and thrombosis.
Authors:
Eric Simone; Bi-Sen Ding; Vladimir Muzykantov
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review     Date:  2008-09-25
Journal Detail:
Title:  Cell and tissue research     Volume:  335     ISSN:  1432-0878     ISO Abbreviation:  Cell Tissue Res.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2008-12-10     Completed Date:  2009-03-18     Revised Date:  2012-04-13    
Medline Journal Info:
Nlm Unique ID:  0417625     Medline TA:  Cell Tissue Res     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  283-300     Citation Subset:  IM    
Affiliation:
Department of Bioengineering, Program in Targeted Therapeutics of Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Engineering and Applied Sciences, Philadelphia, PA, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, Differentiation / metabolism
Drug Carriers / chemistry,  therapeutic use*
Edema / drug therapy,  metabolism,  pathology
Endothelium, Vascular* / metabolism,  physiology
Hemorrhage / drug therapy,  metabolism,  pathology
Humans
Ischemia / drug therapy*,  metabolism,  pathology
Metabolic Diseases / drug therapy,  metabolism,  pathology
Neoplasms / drug therapy,  metabolism,  pathology
Oxidative Stress / drug effects*
Thrombosis / drug therapy*,  metabolism,  pathology
Grant Support
ID/Acronym/Agency:
HL007954/HL/NHLBI NIH HHS; HL078785/HL/NHLBI NIH HHS; HL087036/HL/NHLBI NIH HHS; HL71175/HL/NHLBI NIH HHS; HL73940/HL/NHLBI NIH HHS; R01 HL071175-04/HL/NHLBI NIH HHS; R01 HL073940-04/HL/NHLBI NIH HHS; R01 HL078785-02/HL/NHLBI NIH HHS; R01 HL087036-01A2/HL/NHLBI NIH HHS; R01 HL087036-04/HL/NHLBI NIH HHS; R01 HL087036-05/HL/NHLBI NIH HHS; R01 HL091950-04/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, Differentiation; 0/Drug Carriers
Comments/Corrections

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