title: Sterically stabilized self-assembling reversibly cross-linked polyelectrolyte complexes with nucleic acids for environmental and medical applications.
abstract: One of the principal problems facing nucleic acid delivery systems using polyplexes is the instability of the complexes in the presence of proteins and high salt concentrations. We have used a cross-linking polymer to overcome this problem. Pendant thiol moieties have been incorporated into a PAA (polyamidoamine) homopolymer and a PEG [poly(ethylene glycol)]-PAA-PEG copolymer reported previously as a self-assembling system. When mixed with DNA, small monodisperse sterically stabilized particles are formed in quantitative yields. Optimization of the formulation resulted in nanoparticles which are stable in seawater. This cross-linked formulation has been successfully tested in both freshwater and estuarine field trials as a water tracer. Future work will develop these particles as a groundwater tracer and also for therapeutic applications of nucleic acid delivery.
authors.affiliation: School of Pharmacy, University Park, University of Nottingham, Nottingham NG7 2RD, UK. martin.garnett@nottingham.ac.uk
authors.forename: Martin C
authors.initials: MC
authors.lastname: Garnett
authors.forename: Paolo
authors.initials: P
authors.lastname: Ferruti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ranucci
authors.forename: Marco A
authors.initials: MA
authors.lastname: Suardi
authors.forename: Mieke
authors.initials: M
authors.lastname: Heyde
authors.forename: Rob
authors.initials: R
authors.lastname: Sleat
mesh_terms: D003432:Cross-Linking Reagents / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry; D009696:Nucleic Acids / Q000737:chemistry*; D011073:Polyamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*
chemical_list: D003432:Cross-Linking Reagents; D004337:Drug Carriers; D009696:Nucleic Acids; D011073:Polyamines; D011108:Polymers; D011092:Polyethylene Glycols