Document Detail

In Vitro Investigations of the Efficacy of Cyclodextrin-siRNA Complexes Modified with Lipid-PEG-Octaarginine: Towards a Formulation Strategy for Non-viral Neuronal siRNA Delivery.
MedLine Citation:
PMID:  23192687     Owner:  NLM     Status:  Publisher    
PURPOSE: Development of RNA interference based therapeutics for neurological and neurodegenerative diseases is hindered by a lack of non-viral vectors with suitable properties for systemic administration. Amphiphilic and cationic cyclodextrins (CD) offer potential for neuronal siRNA delivery. We aimed to improve our CD-based siRNA formulation through incorporation of a polyethyleneglycol (PEG) shielding layer and a cell penetrating peptide, octaarginine (R8). METHODS: CD.siRNA complexes were modified by addition of an R8-PEG-lipid conjugate. Physical properties including size, charge and stability were assessed. Flow cytometry was used to determine uptake levels in a neuronal cell model. Knockdown of an exogenous gene and an endogenous housekeeping gene were used to assess gene silencing abilities. RESULTS: CD.siRNA complexes modified with R8-PEG-lipid exhibited a lower surface charge and greater stability to a salt-containing environment. Neuronal uptake was increased and significant reductions in the levels of two target genes were achieved with the new formulation. However, the PEG layer was not sufficient to protect against serum-induced aggregation. CONCLUSIONS: The R8-PEG-lipid-CD.siRNA formulation displayed enhanced salt-stability due to the PEG component, while the R8 component facilitated transfection of neuronal cells and efficient gene silencing. Further improvements will be investigated in the future in order to optimise stability in serum and enhance neuronal specificity.
Aoife M O'Mahony; Stephane Desgranges; Julien Ogier; Aoife Quinlan; Marc Devocelle; Raphael Darcy; John F Cryan; Caitriona M O'Driscoll
Related Documents :
1660527 - Repression of class ii major histocompatibility complex genes by cyclic amp is mediated...
8621457 - Cloning and characterization of the promoter for a potassium channel expressed in high ...
1656497 - Functional analysis of the fic gene involved in regulation of cell division.
2147227 - Transcriptional activation of the rat glucagon gene by the cyclic amp-responsive elemen...
9925587 - Molecular analysis of expression of the lantibiotic pep5 immunity phenotype.
17055757 - The effects of lead and cadmium on gata-1 regulated erythroid gene expression.
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-29
Journal Detail:
Title:  Pharmaceutical research     Volume:  -     ISSN:  1573-904X     ISO Abbreviation:  Pharm. Res.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Pharmacodelivery Group, School of Pharmacy, University College Cork, Cavanagh Pharmacy Building College Rd.,, Cork, Ireland.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

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

Previous Document:  Biochemical toxicology and suicide in Ireland: a laboratory study.
Next Document:  CCR4 expressing cells cultured adherently on a capillary wall and formaldehyde-fixed as the stationa...