Poly(ethylene glycol)-polyethyleneimine NanoGel(TM) particles: Novel drug delivery systems for antisense oligonucleotides

Serguei Vinogradov, Elena Batrakova, Alexander Kabanov

Research output: Contribution to journalArticle

178 Citations (Scopus)

Abstract

A novel type of drug delivery system, termed NanoGel(TM) is proposed. NanoGel(TM) represent particles of a hydrophilic polymer network that were synthesized by cross-linking of polyethyleneimine (PEI) and carbonyldiimidazole-activated poly(ethylene glycol) (PEG) using emulsification/solvent evaporation technique. The resulting NanoGel(TM) was fractionated by gel-permeation chromatography. A major fraction with an average particle size of 120 nm was used in further experiments. Antisense phosphorothioate oligonucleotides (SODN) specific to human mdr1 gene were incorporated in these NanoGel(TM) particles. Loading of NanoGel(TM) particles with SODN resulted in reduction of the particle effective diameter to 80 nm and decreased zeta-potential due to neutralization of the charge of PEI chains by SODN. Accumulation of SODN incorporated in NanoGel(TM) particles in multidrug resistant (MDR) human oral epidermoid carcinoma cells (KBv) was significantly increased compared to the free SODN. Furthermore, efficient transport of SODN-loaded NanoGel(TM) particles across polarized monolayers of human intestinal epithelial cells (Caco-2) was demonstrated. Finally, antisense SODNs incorporated in NanoGel(TM) particles were found to effectively inhibit expression of P-glycoprotein (P-gp) efflux pump in MDR cell lines.

Original languageEnglish (US)
Pages (from-to)291-304
Number of pages14
JournalColloids and Surfaces B: Biointerfaces
Volume16
Issue number1-4
DOIs
StatePublished - Nov 1 1999

Fingerprint

Polyethyleneimine
Ethylene Glycol
oligonucleotides
Antisense Oligonucleotides
Oligonucleotides
Drug Delivery Systems
Polyethylene glycols
glycols
delivery
drugs
ethylene
Cells
Glycoproteins
Emulsification
Gel permeation chromatography
Zeta potential
Monolayers
Evaporation
Genes
Particle size

Keywords

  • Antisense oligonucleotide
  • Hydrogel
  • Multidrug resistance
  • Nanoparticles
  • Poly(ethylene glycol)
  • Polyethyleneimine, Drug delivery

ASJC Scopus subject areas

  • Biotechnology
  • Surfaces and Interfaces
  • Physical and Theoretical Chemistry
  • Colloid and Surface Chemistry

Cite this

Poly(ethylene glycol)-polyethyleneimine NanoGel(TM) particles : Novel drug delivery systems for antisense oligonucleotides. / Vinogradov, Serguei; Batrakova, Elena; Kabanov, Alexander.

In: Colloids and Surfaces B: Biointerfaces, Vol. 16, No. 1-4, 01.11.1999, p. 291-304.

Research output: Contribution to journalArticle

Vinogradov, Serguei ; Batrakova, Elena ; Kabanov, Alexander. / Poly(ethylene glycol)-polyethyleneimine NanoGel(TM) particles : Novel drug delivery systems for antisense oligonucleotides. In: Colloids and Surfaces B: Biointerfaces. 1999 ; Vol. 16, No. 1-4. pp. 291-304.
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