Dexamethasone-Conjugated Polyamidoamine Dendrimer for Delivery of the Heme Oxygenase-1 Gene into the Ischemic Brain

Macromol Biosci. 2015 Jul;15(7):1021-8. doi: 10.1002/mabi.201500058. Epub 2015 May 29.

Abstract

Heme oxygenase-1 (HO-1) has anti-apoptotic and anti-inflammatory effects. In this study, the HO-1 gene was delivered into the brain using dexamethasone-conjugated polyamidoamine generation 2 (PAMAM G2-Dexa) for the treatment of ischemic stroke. PAMAM G2-Dexa formed stable complexes with plasmid DNA (pDNA). The pDNA delivery efficiency of PAMAM G2-Dexa was higher than that of polyethylenimine (PEI25k, 25 kDa), dexamethasone-conjugated PEI (PEI-Dexa), and PAMAM G2 in Neuro2A cells. Therapeutic effect of PAMAM G2-Dexa/pHO-1 complexes was evaluated in a stroke animal model. PAMAM G2-Dexa delivered pHO-1 more efficiently into the ischemic brain than PEI25k and PEI-Dexa with higher therapeutic effect. Therefore, PAMAM G2-Dexa/pHO-1 complexes may be useful for ischemic stroke gene therapy.

Keywords: dexamethasone; gene therapy; heme oxygenase-1; polyamidoamine; stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain Ischemia / therapy*
  • Dendrimers*
  • Dexamethasone*
  • Disease Models, Animal
  • Gene Transfer Techniques*
  • Genetic Therapy*
  • Heme Oxygenase-1 / genetics*
  • Mice
  • Plasmids
  • Polyamines*
  • Rats

Substances

  • Dendrimers
  • Poly(amidoamine)
  • Polyamines
  • Dexamethasone
  • Heme Oxygenase-1