Document Detail


In vivo prevention of arterial restenosis with paclitaxel-encapsulated targeted lipid-polymeric nanoparticles.
MedLine Citation:
PMID:  22087004     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Following recent successes with percutaneous coronary intervention (PCI) for treating coronary artery disease (CAD), many challenges remain. In particular, mechanical injury from the procedure results in extensive endothelial denudation, exposing the underlying collagen IV-rich basal lamina, which promotes both intravascular thrombosis and smooth muscle proliferation. Previously, we reported the engineering of collagen IV-targeting nanoparticles (NPs) and demonstrated their preferential localization to sites of arterial injury. Here, we develop a systemically administered, targeted NP system to deliver an antiproliferative agent to injured vasculature. Approximately 60-nm lipid-polymeric NPs were surface functionalized with collagen IV-targeting peptides and loaded with paclitaxel. In safety studies, the targeted NPs showed no signs of toxicity and a ≥3.5-fold improved maximum tolerated dose versus paclitaxel. In efficacy studies using a rat carotid injury model, paclitaxel (0.3 mg/kg or 1 mg/kg) was i.v. administered postprocedure on days 0 and 5. The targeted NP group resulted in lower neointima-to-media (N/M) scores at 2 wk versus control groups of saline, paclitaxel, or nontargeted NPs. Compared with sham-injury groups, an ∼50% reduction in arterial stenosis was observed with targeted NP treatment. The combination of improved tolerability, sustained release, and vascular targeting could potentially provide a safe and efficacious option in the management of CAD.
Authors:
Juliana M Chan; June-Wha Rhee; Chester L Drum; Roderick T Bronson; Gershon Golomb; Robert Langer; Omid C Farokhzad
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-11-15
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  108     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-30     Completed Date:  2012-01-23     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  19347-52     Citation Subset:  IM    
Affiliation:
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Collagen Type IV / metabolism
Coronary Restenosis / prevention & control*
Immunohistochemistry
Male
Mice
Nanoparticles / therapeutic use*
Neointima / prevention & control*
Paclitaxel / metabolism,  therapeutic use*
Peptides / metabolism
Rats
Rats, Sprague-Dawley
Grant Support
ID/Acronym/Agency:
CA151884/CA/NCI NIH HHS; EB003647/EB/NIBIB NIH HHS; //Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/Collagen Type IV; 0/Peptides; 33069-62-4/Paclitaxel
Comments/Corrections

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


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