Document Detail


Lipid-based nanoparticles for nucleic acid delivery.
MedLine Citation:
PMID:  17252188     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Lipid-based colloidal particles have been extensively studied as systemic gene delivery carriers. The topic that we would like to emphasize is the formulation/assembly of lipid-based nanoparticles (NP) with diameter under 100 nm for delivering nucleic acid in vivo. NP are different from cationic lipid-nucleic acid complexes (lipoplexes) and are vesicles composed of lipids and encapsulated nucleic acids with a diameter less than 100 nm. The diameter of the NP is an important attribute to enable NP to overcome the various in vivo barriers for systemic gene delivery such as: the blood components, reticuloendothelial system (RES) uptake, tumor access, extracellular matrix components, and intracellular barriers. The major formulation factors that impact the diameter and encapsulation efficiency of DNA-containing NP include the lipid composition, nucleic acid to lipid ratio and formulation method. The particle assembly step is a critical one to make NP suitable for in vivo gene delivery. NP are often prepared using a dialysis method either from an aqueous-detergent or aqueous-organic solvent mixture. The resulting particles have diameters about 100 nm and nucleic acid encapsulation ratios are >80%. Additional components can then be added to the particle after it is formed. This ordered assembly strategy enables one to optimize the particle physico-chemical attributes to devise a biocompatible particle with increased gene transfer efficacy in vivo. The components included in the sequentially assembled NP include: poly(ethylene glycol) (PEG)-shielding to improve the particle pharmacokinetic behavior, a targeting ligand to facilitate the particle-cell recognition and in some case a bioresponsive lipid or pH-triggered polymer to enhance nucleic acid release and intracellular trafficking. A number of groups have observed that a PEG-shielded NP is a robust and modestly effective system for systemic gene or small interfering RNA (siRNA) delivery.
Authors:
Weijun Li; Francis C Szoka
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Pharmaceutical research     Volume:  24     ISSN:  0724-8741     ISO Abbreviation:  Pharm. Res.     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-05-31     Completed Date:  2007-09-20     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  438-49     Citation Subset:  IM    
Affiliation:
Departament of Biopharmaceutidal Sciences, School of Pharmacy, University of California at San Francisco, San Francisco, California 94143-0046, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Humans
Lipids / chemistry*
Models, Biological
Nanocapsules / chemistry*
Nucleic Acids / chemistry,  genetics*,  pharmacokinetics
Transfection / methods*
Grant Support
ID/Acronym/Agency:
EB003008/EB/NIBIB NIH HHS; GM61851/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Lipids; 0/Nanocapsules; 0/Nucleic Acids

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


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