Cationic Lipid-Coated Polyplexes (Lipopolyplexes) for DNA and Small RNA Delivery

The delivery of nucleic acids (NA) like DNA for cell transfection or siRNAs for gene knockdown is of major interest for in vitro studies as well as for applications in vivo. The same is true for other small RNA molecules like miRNAs or miRNA inhibitors (antimiRs). Important nonviral gene delivery vectors include liposomes and cationic polymers. With regard to cationic polymers, polyethylenimines (PEIs) are well established for the delivery of NA, by acting as nanoscale delivery platforms (polyplexes). Their combination with liposomes comprising different phospholipids leads to the formation of lipopolyplexes and can further improve their efficacy and biocompatibility, by combining the favorable properties of lipid systems (high stability, efficient cellular uptake, low cytotoxicity) and PEI (NA condensation, facilitated endosomal release).In this chapter, optimal lipopolyplex compositions containing different liposomes and certain branched or linear low-molecular weight PEIs are given. This also includes optimal parameters for lipopolyplex generation, based on various PEIs, N/P ratios, lipids, lipid/PEI ratios, and preparation conditions.Importantly, certain lipopolyplexes retain their biological activity and physicochemical integrity upon prolonged storage at room temperature (RT), in the presence of serum and upon nebulization, thus extending their usefulness toward various applications in vivo.