Linked Life Data

15158966

Source:http://linkedlifedata.com/resource/pubmed/id/15158966

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2004-5-25
pubmed:abstractText
In order to achieve a sustained pharmacological activity of oligonucleotides (ODNs) and avoid repeated administrations, we have developed a new concept of delivery system that combine sustained release and improved intracellular penetration. These systems are designed for the intravitreal delivery of antisense ODNs. The first concept consisted in using liposomes dispersed in a thermosensitive gel (poloxamer 407). After intravitreal administration in a rabbit model, liposomes and liposomes-gel formulations provided, 1-day postinjection, significantly higher drug levels than the control solution of the oligothymidilate pdT16. In addition, there was no significant difference in the amounts of pdT16 found in the vitreous humor between the liposomes and liposomes-gel. Nevertheless, because of their better stability in the absence of poloxamer, liposomes alone allowed to a larger extent to control the delivery of ODNs as compared to liposome-gel formulations since 37% of the ODNs were still found in the vitreous 15 days after administration. In addition, the ODNs found in the vitreous humor were protected against degradation by their encapsulation within liposomes. The second approach consisted in designing microspheres allowing to release in a controlled fashion pdT16. The ODN was encapsulated within poly(lactide-co-glycolide) microspheres alone or associated with polyethylenimine (PEI) at different nitrogen/phosphate (N/P) ratios. The introduction of PEI in the internal aqueous phase resulted in a strong increase of the ODN encapsulation efficiency. PEI affected microsphere morphology inducing the formation of very porous particles yielding to an accelerated release of pdT16. Porosity and controlled delivery was prevented by introducing sodium chloride in the external preparation medium. When incubated with HeLa cells, microspheres encapsulating pdT16/PEI complexes allowed an improvement of the intracellular penetration of the released ODN. Both liposomes and microspheres are suitable for local delivery of ODNs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0378-5173
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
25-30
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Gel and solid matrix systems for the controlled delivery of drug carrier-associated nucleic acids.
pubmed:affiliation
Group of Drug Targeting and Delivery of Poorly Stable Compounds, UMR CNRS 8612, School of Pharmacy, Châtenay-Malabry, France. elias.fattal@cep.u-psud.fr
pubmed:publicationType
Journal Article, Comparative Study