Template-free synthesis and encapsulation technique for layer-by-layer polymer nanocarrier fabrication

The encapsulation of therapeutic molecules within multiple layers of biocompatible and biodegradable polymeric excipients allows exquisite design of their release profile, to the extent the drug can be selectively delivered to a specific target location in vivo. Here, we develop a novel technique for the assembly of multilayer polyelectrolyte nanocarriers based on surface acoustic wave atomization as a rapid and efficient alternative to conventional layer-by-layer assembly, which requires the use of a sacrificial colloidal template over which consecutive polyelectrolyte layers are deposited. Polymer nanocarriers are synthesized by atomizing a polymer solution and suspending them within a complementary polymer solution of opposite charge subsequent to their solidification in-flight as the solvent evaporates; reatomizing this suspension produces nanocarriers with a layer of the second polymer deposited over the initial polymer core. Successive atomization-suspension layering steps can then be repeated to produce as many additional layers as desired. Specifically, we synthesize nanocarriers comprising two and three, and up to eight, alternating layers of chitosan (or polyethyleneimine) and carboxymethyl cellulose within which plasmid DNA is encapsulated and show in vitro DNA release profiles over several days. Evidence that the plasmid's viability is preserved and hence the potential of the technique for gene delivery is illustrated through efficient in vitro transfection of the encapsulated plasmid in human mesenchymal progenitor and COS-7 cells.