Linked Life Data

15760723

Source:http://linkedlifedata.com/resource/pubmed/id/15760723

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2005-3-11
pubmed:abstractText
Antisense oligonucleotides have been used as a specific tool to inhibit the expression of disease associated genes for many years. Unfortunately, oligonucleotides are polyanionic macromolecules which have a weak permeability through biological membranes and are rapidly degraded by nucleases. The purpose of this work is to characterise a new drug delivery system developed by [V. Vogel, D.Lochmann, J. Weyermann, G. Mayer, C. Tziatios, J.A. van der Brock, W. Haase, D. Wouters, U.S. Schubert, J. Kreuter, A. Zimmer, D. Schubert, Oligonucleotide-protamine-albumin nanoparticles preparation, physical properties and intracellular processing, J. Controlled Rel. (in press)] which allows an increased cellular uptake and an intracellular dissociation of the oligonucleotides. The new system based on nanoparticles (NPs) consists of human serum albumin, protamine sulphate and antisense-oligonucleotides (AlPrO). We tested these new nanoparticles on mouse fibroblasts which were stably transfected with a N-methyl-D-aspartate (NMDA) receptor (NR). This cell line enabled us to perform in vitro studies of cellular uptake, intracellular dissociation and effect of the antisense-oligonucleotide in a simple excitotoxicity model. We compared our findings with free oligonucleotides and a commercial available liposomal preparation (DOTAP). We found a 12-fold increased cellular uptake of oligonucleotides in comparison to free oligonucleotides while 100% of the cells were transfected. The AlPrO-NPs showed very low cytotoxic side effects during a 24 h application. We saw an antisense effect of about 35% in a functional assay as well as on the protein level (western blot). The results of the cell penetration and the antisense assay demonstrated that AlPrO nanoparticles are promising carriers for oligonucleotide administration.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0939-6411
pubmed:author
pubmed:issnType
Print
pubmed:volume
59
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
431-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Albumin-protamine-oligonucleotide-nanoparticles as a new antisense delivery system. Part 2: cellular uptake and effect.
pubmed:affiliation
Institute for Pharmaceutical Technology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't