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

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.