title: Development of multicomponent DNA delivery systems based upon poly(amidoamine)-PEG co-polymers.
abstract: PEGylated polyamidoamine (PAA) polymers were investigated for the production of sterically stabilised DNA delivery systems. Comparison of a PEGylated polymer (NG47) with a non-PEGylated polymer (NG49) showed similar binding of co-polymer to DNA by displacement of ethidium bromide (EB) and DNA melting studies. Gel electrophoresis, turbidimetric analysis and PCS demonstrated differences in the colloidal properties of the complexes, which were attributable to the formation of soluble complexes by the PEGylated co-polymer. However, transmission electron microscopy (TEM) showed that the resulting complexes containing poly(ethylene glycol) (PEG) were not well condensed, susceptible to degradation by nucleases, and thus not suited for in vivo delivery. The poor properties of the PEGylated co-polymer were attributed to an excess of PEG. However, polymer blends of NG47 and NG49 at defined ratios of polymer to co-polymer and total repeating units (RUs) to nucleotide, spontaneously formed complexes with a range of desirable properties. These included small size and polydispersity, high particle density, low surface charge and resistance to nuclease degradation. Complexes made with PEGylated polymer alone, and the polymer blends both suffered from a reduced polyfection activity. This was attributed to a low surface charge on the complex, which reduced interactions with the cell membrane and consequent uptake of the particles into the cell.
authors.affiliation: School of Pharmaceutical Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Rackstraw
authors.forename: Snjezana
authors.initials: S
authors.lastname: Stolnik
authors.forename: Stanley S
authors.initials: SS
authors.lastname: Davis
authors.forename: Fabio
authors.initials: F
authors.lastname: Bignotti
authors.forename: Martin C
authors.initials: MC
authors.lastname: Garnett
mesh_terms: D000818:Animals; D002460:Cell Line; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D003850:Deoxyribonuclease I / Q000378:metabolism; D016503:Drug Delivery Systems; D005029:Ethylenediamines / Q000737:chemistry; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D015394:Molecular Structure; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000378:metabolism*; D011108:Polymers / Q000737:chemistry / Q000378:metabolism*; D013696:Temperature
chemical_list: D005029:Ethylenediamines; C464520:PEGylated polymer NG47; D011108:Polymers; C027450:dimethylethylenediamine; D011092:Polyethylene Glycols; D004247:DNA; D003850:Deoxyribonuclease I