Impact of Lipid Substitution on Assembly and Delivery of siRNA by Cationic Polymers

Characterization of a polymer library engineered to enhance their ability to protect and deliver their nucleotide cargo to the cells is reported. The ζ-potential continuously increased with higher polymer:siRNA weight ratio, and the ζ-potential of lipid-modified polymers:siRNA complexes were higher than PEI2 at all ratios. At polymer:siRNA ratio of 1:1, all lipid-substituted polymers showed complete protection against degradation. Lipid-modified polymers significantly increased the cellular uptake of siRNA complexes and down-regulation of GAPDH and P-gp (max. 66% and 67%, respectively). The results indicate that hydrophobic modification of low molecular PEI could render this otherwise ineffective polymer to a safe effective delivery system for intracellular siRNA delivery and protein silencing.