PEG–PCL–DEX polymersome–protamine vector as an efficient gene delivery system via PEG-guided self-assembly

Abstract

Aim: The nonviral carrier system based on the triblock copolymer PEG–PCL–DEX (PPD) and protamine was developed for nucleic acid delivery. Materials & methods: Self-assembly occurred in the PEG continuous phase to form ‘dextran–interior’ polymersomes. siRNA can be condensed by protamine and encapsulated into PPD polymersomes in order to form the PPD–protamine siRNA nanoparticles by thermodynamically preferential partition between the PEG continuous phase and the dextran cavity. Results: This system can package siRNA into PPD polymersomes to form 145.2 ± 8.02-nm (± standard deviation) nanoparticles, and the ζ-potential can be reduced to approximately 0 mV. PPD–protamine siRNA nanoparticles achieved cellular uptake of siRNA in SMMC-7721 cells with negligible cytotoxicity, and the GL3 gene expression can be reduced to 61.73 ± 6.25%. A biodistribution study of nanoparticles suggested that the PPD–protamine siRNA nanoparticles mainly accumulated in liver. Conclusion: All of these results suggest that PPD–protamine carriers may offer a promising gene delivery strategy for the treatment of liver-related disease. Original submitted 14 September 2012; Revised submitted 21 March 2013