Nanocomposites of lung surfactant and biodegradable cationic nanoparticles improve transfection efficiency to lung...

The objective of this study was to develop highly efficient ternary nanocomposites for aerosol gene therapy consisting of a biodegradable polymer core, poly[vinyl-3-(diethylamino)propylcarbamate-co-vinyl acetate-co-vinyl alcohol]-graft-poly(d,l-lactide-co-glycolide), pDNA and a third component to alter surface properties, physicochemical characteristics and biological activity. The effects of the surface altering components lung surfactant, carboxymethyl cellulose (CMC) or poloxamer on nanocomposites were characterized with regard to size, zeta potential, cytotoxicity, biological activity and surface properties. With increasing concentrations of lung surfactant, CMC or poloxamer, sizes of nanocomposites increased. AFM nanoindentation measurements showed a significant increase in adhesion forces of nanocomposites compared to pure nanoparticles. Zeta potential values, cytotoxicity and intracellular uptake demonstrated a strong dependency on the surface altering component. While an excess of CMC led to a decreased uptake into cells due to the negative zeta potential, nanocomposites with lung surfactant displayed enhanced intracellular uptake. Transfection efficiency of nanocomposites with lung surfactant was 12-fold higher compared to pure nanoparticles and 30-fold higher compared to polyethylenimine in lung cells and could also be maintained after nebulization. Ternary nanocomposites prepared with lung surfactant proved to be a potent pulmonary gene delivery vector due to its high stability during aerosolization with a vibrating mesh nebulizer and favourable biological activity.