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Characterization and in vivo performance of dextran–spermine polyplexes and DOTAP/cholesterol lipoplexes administered locally and systemically

Paper ID Volume ID Publish Year Pages File Format Full-Text
11104 718 2007 11 PDF Available
Title
Characterization and in vivo performance of dextran–spermine polyplexes and DOTAP/cholesterol lipoplexes administered locally and systemically
Abstract

In this study, we compared two systems which can be applied for transfection in vitro and in vivo: polyplexes based on the polymer dextran–spermine (D–SPM) and lipoplexes based on 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)/cholesterol. The carriers differ in (1) solubility in aqueous media, (2) source of the positive charges (quaternary amines for DOTAP and primary plus secondary amines for D–SPM), (3) electrostatics, i.e., for lipid and polymer, respectively: zeta-potential (81.0 and 48.1 mV), surface potential (180 and 92 mV), and surface pH (10.47 and 8.97), and (4) charge distribution (ordered versus non-ordered). The stability of the complex upon interaction with serum proteins was studied by means of fluorescence resonance energy transfer (FRET) between rhodamine-labeled cationic carriers and fluorescein-labeled DNA. Addition of serum increases the lipid–DNA average distance and decreases the polymer–DNA distance. However, FRET efficiency indicates that serum proteins do not induce a major DNA dissociation for either polyplexes or lipoplexes. Comparing the biodistribution of rhodamine-labeled complexes and the transgene expression after intravenous (i.v.), intramuscular (i.m.), and intranasal (i.n.) administration, we found that local administration of lipoplexes resulted in the lipoplexes remaining at the site of injection, whereas the polyplexes showed systemic distribution, accompanied by transgene expression in lungs and liver. It is suggested that the high water-solubility of the polymer combined with its lower positive charge (compared to DOTAP), which makes its association with the cells at the site of injection weaker, enables the polymer to reach and transfect distant organs through the blood stream. Using chemically modified D–SPM, we demonstrated the importance of high density of positive charges and a sufficient level of secondary amines for achieving efficient transgene expression in vivo.

Keywords
Gene delivery; Charge-distribution; PEGylation; Biodistribution; Transgene expression
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Characterization and in vivo performance of dextran–spermine polyplexes and DOTAP/cholesterol lipoplexes administered locally and systemically
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 28, Issue 14, May 2007, Pages 2339–2349
Authors
, , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us