Linked Life Data

17614155

Source:http://linkedlifedata.com/resource/pubmed/id/17614155

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2007-8-3
pubmed:abstractText
Novel cationic pentablock copolymers based on poly(2-diethylaminoethylmethacrylate) (PDEAEM) and Pluronic F127 were evaluated as non-viral gene delivery vectors from a physiochemical point of view for stability and transfection efficiency in complete growth media. A novel strategy was introduced to sterically stabilize the polyplexes of such Pluronic-based cationic polymers against aggregation with serum proteins. As cationic pentablock copolymers condense plasmid DNA into nanoplexes of 100-150 nm diameter, unmodified Pluronic added to the formulation self-assemble with the pentablock copolymers on the surface of polyplexes and shield the cationic PDEAEM chains of pentablock copolymers sterically with its long poly(ethyleneoxide) chains. These coated polyplexes formed colloidally stable dispersions of 150-250 nm diameter in serum-supplemented buffers. Cryo-TEM micrographs also showed that coating polyplexes with unmodified Pluronic reduced aggregation in serum proteins. Pentablock copolymers preserved the integrity of plasmid DNA condensed inside the polyplexes and provided efficient resistance to its degradation by nucleases. Though the total amount of DNA retained by ExGen 500 polyplexes after nuclease digestion was more than that retained by pentablock copolymers, the amount of plasmid retained in supercoiled form was not significantly different. Polyplexes coated with unmodified Pluronic provided efficient transfection in SKOV3 cells in complete growth media, comparable to that provided by ExGen 500 in terms of number of cells transfected, and one order less in terms of total transgene protein expressed. These sterically shielded polyplexes also exhibited much lower cytotoxicities than uncoated polyplexes of pentablock copolymers, and significantly lower than the cytotoxicity of ExGen 500 at relevant concentrations. This colloidally stable, versatile, multi-component gene delivery system also forms thermo-reversible injectable hydrogels like Pluronics at physiological temperatures that can be used for sustained delivery of polyplexes, and is promising for systemic applications.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1873-4995
pubmed:author
pubmed:issnType
Electronic
pubmed:day
16
pubmed:volume
121
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
28-37
pubmed:meshHeading
pubmed-meshheading:17614155-Buffers, pubmed-meshheading:17614155-Cell Line, Tumor, pubmed-meshheading:17614155-Cell Survival, pubmed-meshheading:17614155-Colloids, pubmed-meshheading:17614155-Culture Media, pubmed-meshheading:17614155-Female, pubmed-meshheading:17614155-Gene Transfer Techniques, pubmed-meshheading:17614155-Genes, Reporter, pubmed-meshheading:17614155-Green Fluorescent Proteins, pubmed-meshheading:17614155-Humans, pubmed-meshheading:17614155-Hydrogen-Ion Concentration, pubmed-meshheading:17614155-Light, pubmed-meshheading:17614155-Luciferases, pubmed-meshheading:17614155-Materials Testing, pubmed-meshheading:17614155-Methacrylates, pubmed-meshheading:17614155-Microscopy, Electron, Transmission, pubmed-meshheading:17614155-Ovarian Neoplasms, pubmed-meshheading:17614155-Poloxamer, pubmed-meshheading:17614155-Polymers, pubmed-meshheading:17614155-Scattering, Radiation, pubmed-meshheading:17614155-Temperature
pubmed:year
2007
pubmed:articleTitle
Colloidally stable novel copolymeric system for gene delivery in complete growth media.
pubmed:affiliation
Department of Chemical Engineering, Iowa State University, 3035 Sweeny Hall, Ames, IA 50011-2230, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't