title: Self-assembly of polyamine-poly(ethylene glycol) copolymers with phosphorothioate oligonucleotides.
abstract: The cationic copolymers for DNA delivery were synthesized by conjugating poly(ethylene glycol) (PEG) and polyamines: polyspermine (PSP) and polyethyleneimine (PEI). These molecules spontaneously form electrostatic complexes with a model 24-mer phoshorothioate oligonucleotide, T24 (PS-ODN). The copolymer complexes are water soluble. This is a marked contrast with the complexes formed by nonmodified PSP and PEI, which immediately precipitate out of solution. The potentiometric titration study suggests that the amino groups of the copolymers form a cooperative system of salt bonds with the thiophosphate groups of the PS-ODN. The PEG-PEI complexes are stable at physiological pH and ionic strengths. The PEG-PSP complexes are less stable in the presence of the low molecular mass electrolytes compared to the PEG-PEI complexes. The dynamic light scattering and transmission electron microscopy demonstrate that the complex particles are small-ca. 12 nm for PEG-PSP and ca. 32 nm for PEG-PEI. They can be lyophilized and redissolved or stored in solution for up to several months without changing size. The study suggests that as a result of formulation with the PEG-PEI the interactions of PS-ODNs with serum proteins (using the example of bovine serum albumin) are decreased and PS-ODN is protected against nuclease degradation. The simplicity of preparation and long shelf life make these systems attractive as potential pharmaceutical formulations for oligonucleotides.
authors.affiliation: Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 600 South 42nd Street, Omaha, Nebraska 68198, USA.
authors.forename: S V
authors.initials: SV
authors.lastname: Vinogradov
authors.forename: T K
authors.initials: TK
authors.lastname: Bronich
authors.forename: A V
authors.initials: AV
authors.lastname: Kabanov
mesh_terms: D001798:Blood Proteins / Q000737:chemistry; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003851:Deoxyribonucleases / Q000737:chemistry; D008970:Molecular Weight; D009841:Oligonucleotides / Q000138:chemical synthesis*; D009946:Organothiophosphorus Compounds / Q000737:chemistry*; D011073:Polyamines / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011199:Potentiometry; D011485:Protein Binding; D013050:Spectrometry, Fluorescence; D013096:Spermine / Q000737:chemistry
chemical_list: D001798:Blood Proteins; D009841:Oligonucleotides; D009946:Organothiophosphorus Compounds; D011073:Polyamines; D011108:Polymers; D013096:Spermine; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D003851:Deoxyribonucleases