Sterically stabilized self-assembling reversibly cross-linked polyelectrolyte complexes with nucleic acids for environmental and medical applications.
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.
Garnett
Martin C
MC
School of Pharmacy, University Park, University of Nottingham, Nottingham NG7 2RD, UK. martin.garnett@nottingham.ac.uk
Ferruti
Paolo
P
Ranucci
Elisabetta
E
Suardi
Marco A
MA
Heyde
Mieke
M
Sleat
Rob
R
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*
D003432:Cross-Linking Reagents; D004337:Drug Carriers; D009696:Nucleic Acids; D011073:Polyamines; D011108:Polymers; D011092:Polyethylene Glycols