Improved gene transfection efficacy and cytocompatibility of multifunctional polyamidoamine-cross-linked hyaluronan particles.

We describe a multi-functional, cationic hyaluronic acid (HA)-based gene carrier with improved transfection over non-cross-linked HA, and negligible cytotoxicity. Cationized particles are developed by cross-linking HA chain carboxyl groups with polyamidoamine amine termini to produce well segregated particles of 350-400 nm with a surface charge density of +2 mV, compared with -35 mV for non-cationized particles. A tethered antibody fragment retains ligand binding for cell targeting. Cationized and antibody-linked particles complex plasmid DNA efficiently and the cationized particles successfully deliver reporter genes to bovine intervertebral disk cells as an intervertebral disk regeneration model.