Nanosized cationic hydrogels for drug delivery: Preparation, properties and interactions with cells

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

Research output: Contribution to journalArticle

591 Scopus citations

Abstract

A new family of nanoscale materials on the basis of dispersed networks of cross-linked ionic and nonionic hydrophilic polymers is being developed. One example is the nanosized cationic network of cross-linked poly(ethylene oxide) (PEO) and polyethyleneimine (PEI), PEO-cl-PEI nanogel. Interaction of anionic amphiphilic molecules or oligonucleotides with PEO-cl-PEI results in formation of nanocomposite materials in which the hydrophobic regions from polyion-complexes are joined by the hydrophilic PEO chains. Formation of polyion-complexes leads to the collapse of the dispersed gel particles. However, the complexes form stable aqueous dispersions due to the stabilizing effect of the PEO chain. These systems allow for immobilization of negatively charged biologically active compounds such as retinoic acid, indomethacin and oligonucleotides (bound to polycation chains) or hydrophobic molecules (incorporated into nonpolar regions of polyion-surfactant complexes). The nanogel particles carrying biological active compounds have been modified with polypeptide ligands to enhance receptor-mediated delivery. Efficient cellular uptake and intracellular release of oligonucleotides immobilized in PEO-cl-PEI nanogel have been demonstrated. Antisense activity of an oligonucleotide in a cell model was elevated as a result of formulation of oligonucleotide with the nanogel. This delivery system has a potential of enhancing oral and brain bioavailability of oligonucleotides as demonstrated using polarized epithelial and brain microvessel endothelial cell monolayers.

Original languageEnglish (US)
Pages (from-to)135-147
Number of pages13
JournalAdvanced Drug Delivery Reviews
Volume54
Issue number1
DOIs
StatePublished - Jan 17 2002

    Fingerprint

Keywords

  • Drug delivery
  • Drug targeting
  • Formulation
  • Nanogel
  • Poly(ethylene glycol)
  • Polyethyleneimine
  • Polynucleotides

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this