Self-assembly of polyamine-poly(ethylene glycol) copolymers with phosphorothioate oligonucleotides

Serguei V. Vinogradov, Tatiana K Bronich, Alexander V. Kabanov

Research output: Contribution to journalArticle

239 Citations (Scopus)

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 phosphorothioate 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.

Original languageEnglish (US)
Pages (from-to)805-812
Number of pages8
JournalBioconjugate Chemistry
Volume9
Issue number6
DOIs
StatePublished - Nov 1 1998

Fingerprint

Phosphorothioate Oligonucleotides
Polyethyleneimine
Ethylene Glycol
Oligonucleotides
Polyamines
Self assembly
Polyethylene glycols
Copolymers
Drug Compounding
Bovine Serum Albumin
Static Electricity
Transmission Electron Microscopy
Osmolar Concentration
Electrolytes
Blood Proteins
Molecular mass
Dynamic light scattering
Light transmission
Salts
Ionic strength

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

Cite this

Self-assembly of polyamine-poly(ethylene glycol) copolymers with phosphorothioate oligonucleotides. / Vinogradov, Serguei V.; Bronich, Tatiana K; Kabanov, Alexander V.

In: Bioconjugate Chemistry, Vol. 9, No. 6, 01.11.1998, p. 805-812.

Research output: Contribution to journalArticle

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