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Complexation to Cationic Microspheres of Double-Stranded Peptide Nucleic Acid-DNA Chimeras Exhibiting Decoy Activity.
- Source :
- Journal of Biomedical Science; Sep/Oct2004, Vol. 11 Issue 5, p697-704, 8p, 1 Color Photograph, 3 Diagrams, 2 Graphs
- Publication Year :
- 2004
-
Abstract
- The major aim of this paper was to determine whether cationic microspheres (CM), consisting of the permeable polymer Eudragit<superscript>®</superscript> RS 100 plus the cationic surfactant dioctadecyl-dimethyl-ammonium bromide (DDAB<subscript>18</subscript>), could bind to double-stranded peptide nucleic acid PNA-DNA-PNA (PDP) chimeras exhibiting decoy activity against NF-κB transcription factors. Microspheres were produced by the ‘solvent evaporation method’ and centrifugation at 500, 1,000 and 3,000 rpm to obtain different-sized microparticles. Microsphere morphology, size and size distribution were determined by optical and electron microscopy observations. In order to determine their binding activity, double-stranded DNA-based and PDP-based decoy molecules were incubated with different amounts of microparticles in the presence of 100 ng of either <superscript>32</superscript>P-labeled DNA-DNA or DNA-PDP hybrid molecules or cold PDP-PDP hybrids. The complexes were analyzed by agarose gel electrophoresis. The resistance of <superscript>32</superscript>P-labeled DNA-DNA and DNA-PDP molecules in the presence of serum or cellular extracts was evaluated after binding to CM by gel electrophoresis analysis. DDAB<subscript>18</subscript> Eudragit RS 100 microspheres are able to bind to DNA-PDP and PDP-PDP hybrids, to deliver these molecules to target cells and to protect DNA-PDP molecules from enzymatic degradation in simulated biological fluids. In addition, when assayed in ex vivo conditions, DDAB<subscript>18</subscript> Eudragit RS 100 microspheres exhibited low toxicity. The results presented in this paper demonstrate that CM can be considered suitable formulations for pharmacogenomic therapy employing double-stranded PDP chimeras. Copyright © 2004 National Science Council, ROC and S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
- Subjects :
- NUCLEIC acids
DNA
CHIMERAS (Botany)
MICROSPHERES
GENE therapy
Subjects
Details
- Language :
- English
- ISSN :
- 10217770
- Volume :
- 11
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Journal of Biomedical Science
- Publication Type :
- Academic Journal
- Accession number :
- 14220585
- Full Text :
- https://doi.org/10.1007/BF02256136