Dexamethasone conjugation to polyamidoamine dendrimers G1 and G2 for enhanced transfection efficiency with an anti-inflammatory effect

J Drug Target. 2012 Sep;20(8):667-77. doi: 10.3109/1061186X.2012.712127.

Abstract

Polyamidoamine (PAM) dendrimers with low generation such as PAM generation 1 (PAMG1) and PAM generation 2 (PAMG2) have been widely used as a gene carrier due to low toxicity, albeit their low transfection efficiency. In this study, dexamethasone was conjugated to PAMG1 and PAMG2 in order to increase the transfection efficiency. In a gel retardation assay, the dexamethasone conjugated PAMG1 and PAMG2 (PAMG1-Dexa and PAMG2-Dexa) retarded plasmid DNA (pDNA) completely at 5:1 and 3:1 weight ratios (polymer:pDNA), respectively. In transfection assays, PAMG1-Dexa and PAMG2-Dexa had the highest transfection efficiency at 20:1 and 10:1 weight ratios, respectively. In addition, PAMG1-Dexa and PAMG2-Dexa had higher transfection efficiencies than PAMG1, PAMG2, PEI25k, and lipofectamine. In a MTT assay, PAMG1-Dexa and PAMG2-Dexa were less cytotoxic than lipofectamine. In addition, PAMG1-Dexa and PAMG2-Dexa decreased the TNF-α level more efficiently than dexamethasone only in the lipopolysaccharide (LPS)-induced Raw264.7 cells. Therefore, PAMG1-Dexa and PAMG2-Dexa may prove to be useful as gene delivery carriers with an anti-inflammatory effect.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / chemistry*
  • Cell Line, Tumor
  • Cells, Cultured
  • DNA / genetics
  • Dendrimers / administration & dosage
  • Dendrimers / chemistry*
  • Dexamethasone / administration & dosage*
  • Dexamethasone / chemistry*
  • Gene Transfer Techniques
  • Genetic Therapy / methods
  • HEK293 Cells
  • Humans
  • Lipids / administration & dosage
  • Mice
  • Plasmids / genetics
  • Polyamines / administration & dosage
  • Polyamines / chemistry*
  • Transfection / methods*
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Anti-Inflammatory Agents
  • Dendrimers
  • Lipids
  • Lipofectamine
  • Poly(amidoamine)
  • Polyamines
  • Tumor Necrosis Factor-alpha
  • Dexamethasone
  • DNA