Document Detail


Vitamin E TPGS-emulsified poly(lactic-co-glycolic acid) nanoparticles for cardiovascular restenosis treatment.
MedLine Citation:
PMID:  17716178     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIMS: Paclitaxel is one of the most effective antiproliferative agents and it has been applied in the development of drug-eluting stents. There are difficulties, however, in using paclitaxel in clinical applications owing to its poor solubility and side effects. We have synthesized nanoparticles of biodegradable polymers for the effective and sustainable delivery of paclitaxel and other antiproliferative agents for restenosis treatment. METHODS & RESULTS: Paclitaxel-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles were prepared by a modified solvent extraction/evaporation method with D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) or polyvinyl alcohol (PVA) as an emulsifier. Drug-loaded nanoparticles were characterized for size and size distribution, surface morphology, surface charge, drug-encapsulation efficiency and in vitro drug-release kinetics. Cellular uptake of fluorescent nanoparticles was investigated in vitro in coronary artery smooth muscle cells and in vivo in the carotid arteries of rabbits. The antiproliferative effects of the nanoparticle formulations were assessed in vitro in close comparison with Taxol((R)). Both the PVA- and TPGS-emulsified nanoparticles have similar size and size distribution, surface morphology and dispersion stability and showed great advantages over paclitaxel in in vitro cellular uptake and cytotoxicity than Taxol. The TPGS-emulsified nanoparticle formulation has higher drug-encapsulation efficiency, cellular uptake and cytotoxicity than the PVA-emulsified nanoparticle formulation. IC(50) in 24-h culture with coronary artery smooth muscle cells is 748 ng/ml for paclitaxel, 708 ng/ml for PVA-emulsified nanoparticles and 474 ng/ml for TPGS-emulsified nanoparticles, respectively. CONCLUSION: TPGS-emulsified PLGA nanoparticles have great potential for the effective and sustainable delivery of antiproliferative agents and for the development of nanoparticle-coated stents, which may become the third generation of cardiovascular stents.
Authors:
Si-Shen Feng; Wutao Zeng; Yean Teng Lim; Lingyun Zhao; Khin Yin Win; Reida Oakley; Swee Hin Teoh; Ronald Chi Hang Lee; Shirong Pan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nanomedicine (London, England)     Volume:  2     ISSN:  1748-6963     ISO Abbreviation:  Nanomedicine (Lond)     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-08-24     Completed Date:  2007-09-18     Revised Date:  2010-01-28    
Medline Journal Info:
Nlm Unique ID:  101278111     Medline TA:  Nanomedicine (Lond)     Country:  England    
Other Details:
Languages:  eng     Pagination:  333-44     Citation Subset:  IM    
Affiliation:
Department of Chemical & Biomolecular Engineering, National University of Singapore, Singapore. chefss@nus.edu.sg
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MeSH Terms
Descriptor/Qualifier:
Animals
Delayed-Action Preparations / administration & dosage*,  chemistry*
Drug Carriers / chemistry
Drug Compounding / methods
Emulsions / chemistry
Graft Occlusion, Vascular / pathology*,  prevention & control*
Lactic Acid / chemistry*
Nanomedicine / methods
Nanoparticles / chemistry,  therapeutic use*,  ultrastructure
Particle Size
Polyglycolic Acid / chemistry*
Polymers / chemistry*
Rabbits
Treatment Outcome
Vitamin E / administration & dosage*,  chemistry
Chemical
Reg. No./Substance:
0/Delayed-Action Preparations; 0/Drug Carriers; 0/Emulsions; 0/Polymers; 0/polylactic acid-polyglycolic acid copolymer; 1406-18-4/Vitamin E; 26009-03-0/Polyglycolic Acid; 50-21-5/Lactic Acid

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


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