Document Detail


Enhancement of surface ligand display on PLGA nanoparticles with amphiphilic ligand conjugates.
MedLine Citation:
PMID:  21723893     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Biodegradable polymeric nanoparticles are widely recognized as efficacious drug delivery vehicles, yet the rational engineering of nanoparticle surfaces in order to improve biodistribution, reduce clearance, and/or improve targeting remains a significant challenge. We have previously demonstrated that an amphiphilic conjugate of avidin and palmitic acid can be used to modify poly(lactic-co-glycolic acid) (PLGA) particle surfaces to display functional avidin groups, allowing for the facile attachment of biotinylated ligands for targeting or steric stabilization. Here, we hypothesized that the incorporation, density, and stability of surface-presented avidin could be modulated through varying the lipophilicity of its fatty acid conjugate partner. We tested this hypothesis by generating a set of novel conjugates incorporating avidin and common fatty acids. We found that conjugation to linoleic acid resulted in a ~60% increase in the incorporation of avidin on the nanoparticle surface compared to avidin-palmitic acid, which exhibited the highest avidin incorporation in previous studies. Further, the linoleic acid-avidin conjugate yielded nanoparticles with enhanced ability to bind biotinylated ligands compared to the previous method; nanoparticles modified with avidin-linoleic acid bound ~170% more biotin-HRP than those made with avidin-palmitic acid and ~1300% more than particles made without conjugated avidin. Most critically, increased ligand density on anti-CD4-targeted nanoparticles formulated with the linoleic acid-avidin conjugate resulted in a 5% increase in binding of CD4(+) T cells. Thus we conclude that the novel avidin-linoleic acid conjugate facilitates enhanced ligand density on PLGA nanoparticles, resulting in functional enhancement of cellular targeting.
Authors:
Jason Park; Thomas Mattessich; Steven M Jay; Atu Agawu; W Mark Saltzman; Tarek M Fahmy
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-06-24
Journal Detail:
Title:  Journal of controlled release : official journal of the Controlled Release Society     Volume:  156     ISSN:  1873-4995     ISO Abbreviation:  J Control Release     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-14     Completed Date:  2012-05-14     Revised Date:  2013-10-22    
Medline Journal Info:
Nlm Unique ID:  8607908     Medline TA:  J Control Release     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  109-15     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier B.V. All rights reserved.
Affiliation:
Yale University, Department of Biomedical Engineering, 55 Prospect Street, New Haven, CT 06511, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Avidin / chemistry
Biocompatible Materials / chemistry*
CD4-Positive T-Lymphocytes / drug effects
Cells, Cultured
Drug Carriers / chemistry*
Drug Stability
Fluorescein-5-isothiocyanate / administration & dosage,  analogs & derivatives,  chemistry,  pharmacology
Lactic Acid / chemistry*
Ligands
Mice
Microscopy, Electron, Scanning
Nanoparticles / chemistry*
Palmitic Acid / chemistry
Particle Size
Polyglycolic Acid / chemistry*
Serum Albumin, Bovine / administration & dosage,  chemistry,  pharmacology
Spleen / cytology,  drug effects
Surface Properties
Surface-Active Agents / chemistry*
Grant Support
ID/Acronym/Agency:
EB000487/EB/NIBIB NIH HHS; K99 HL112905/HL/NHLBI NIH HHS; R01 EB000487/EB/NIBIB NIH HHS
Chemical
Reg. No./Substance:
0/Biocompatible Materials; 0/Drug Carriers; 0/Ligands; 0/Serum Albumin, Bovine; 0/Surface-Active Agents; 0/fluorescein isothiocyanate bovine serum albumin; 0/polylactic acid-polyglycolic acid copolymer; 1405-69-2/Avidin; 26009-03-0/Polyglycolic Acid; 3326-32-7/Fluorescein-5-isothiocyanate; 50-21-5/Lactic Acid; 57-10-3/Palmitic Acid
Comments/Corrections

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