Linked Life Data

16298011

Source:http://linkedlifedata.com/resource/pubmed/id/16298011

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2005-12-7
pubmed:abstractText
A stable, freeze-dried formulation consisting of a core-shell-type polyplex with a poly(ethylene glycol) (PEG) shell (polyplex micelles) was prepared from a polyion complex of plasmid DNA (pDNA) and thiolated PEG-poly(L-lysine) block copolymers. The use of lyoprotectants was avoided by crosslinking the core with disulfide bonds. The crosslinked polyplex micelles (CPMs) showed excellent stability during freeze-drying and reconstitution processes, which is in sharp contrast with the formation of visible agglomerates from the non-crosslinked polyplex micelles (NCPMs) after a similar process. A thiolation degree higher than 13% of the lysine residues was required to achieve sufficient tolerability of the CPMs during the freeze-drying/reconstitution cycle. Dynamic light scattering measurements and atomic force microscopy observations demonstrated that the original size and shape of the CPMs with a thiolation degree of higher than 13% were maintained even after the freeze-drying. Furthermore, the CPMs reconstituted from the freeze-dried state achieved a transfection efficiency as high as that of the original samples. The intravenous injection of the CPM with a thiolation degree of 37% into mice via the orbital vein led to an appreciably uniform gene expression of a yellow fluorescence protein variant (Venus) in the liver, while no gene expression was observed in the case of the free pDNA injection. The procedure of disulfide crosslinking of the polyplex micell core allows the preparation of non-viral gene vectors as a powder formulation without the use of any lyoprotectants. This achievement is certainly useful for pharmaceutical applications and exhibits many advantages, including easy concentration adjustments of dosing samples, long-term storage stability, and large-scale production reproducibility.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0168-3659
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
109
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
15-23
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16298011-Animals, pubmed-meshheading:16298011-Cell Line, pubmed-meshheading:16298011-Chemistry, Pharmaceutical, pubmed-meshheading:16298011-Cross-Linking Reagents, pubmed-meshheading:16298011-DNA, pubmed-meshheading:16298011-Disulfides, pubmed-meshheading:16298011-Drug Screening Assays, Antitumor, pubmed-meshheading:16298011-Excipients, pubmed-meshheading:16298011-Freeze Drying, pubmed-meshheading:16298011-Gene Transfer Techniques, pubmed-meshheading:16298011-Humans, pubmed-meshheading:16298011-Light, pubmed-meshheading:16298011-Liver, pubmed-meshheading:16298011-Luciferases, pubmed-meshheading:16298011-Micelles, pubmed-meshheading:16298011-Microscopy, Atomic Force, pubmed-meshheading:16298011-Particle Size, pubmed-meshheading:16298011-Polyethylene Glycols, pubmed-meshheading:16298011-Polylysine, pubmed-meshheading:16298011-Scattering, Radiation, pubmed-meshheading:16298011-Solubility, pubmed-meshheading:16298011-Spectrophotometry, Ultraviolet, pubmed-meshheading:16298011-Transfection
pubmed:year
2005
pubmed:articleTitle
Freeze-dried formulations for in vivo gene delivery of PEGylated polyplex micelles with disulfide crosslinked cores to the liver.
pubmed:affiliation
Department of Materials Science and Engineering, Graduate School of Engineering, The University of Tokyo, Bunkyo-ku, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't