ABSTRACT

BPEI/pDNA and LPEI/siRNA, which were too stable and too unstable, respectively, did not serve as efcient carriers. siRNA, being a very small molecule, showed limited interactions with LPEI (Zhang et al. 2008). The stability of self-assembled polyplexes of siRNA could be improved by introducing cross-links between the incorporated cysteine groups within the polymer. The larger DNA molecule allows extensive electrostatic interactions with the cationic polymers conferring sufcient stability to the polyplexes without further cross-linking. For systemic administration, polyplex nanomicelles can be formed based on the self-organization of amphiphilic block copolymers composed of a polyethylene glycol (PEG) or any hydrophilic block and a cationic polymer segment, which forms the core by condensing with nucleic acid while the former, with its presence on the surface, prevents destabilization by hindering nonspecic interactions with blood components, such as nuclease and opsonins (Itaka and Kataoka 2011) (Figures 8.1 and 8.2).