Amphiphilic Chitosan Bearing Double Palmitoyl Chains and Quaternary Ammonium Moieties as a Nanocarrier for Plasmid DNA

Abstract

Amphiphilic chitosan, bPalm-CS-HTAP, having <i>N</i>-(2-((2,3-bis(palmitoyloxy)propyl)amino)-2-oxoethyl) (bPalm) groups as double hydrophobic tails and <i>O</i>-[(2-hydroxyl-3-trimethylammonium)] propyl (HTAP) groups as hydrophilic heads was synthesized and evaluated for its self-assembly properties and potential as a gene carrier. The degree of bis-palmitoyl group substitution (<i>DS</i> _bPalm) and the degree of quaternization (<i>DQ</i>) were approximately 2 and 56%, respectively. bPalm-CS-HTAP was found to assemble into nanosized spherical particles with a hydrodynamic diameter (<i>D</i> _H) of 265.5 ± 7.40 nm (PDI = 0.5) and a surface charge potential of 40.1 ± 0.04 mV. bPalm-CS-HTAP condensed the plasmid pVAX1.CoV2RBDme completely at a bPalm-CS-HTAP:pDNA ratio of 2:1. The self-assembled bPalm-CS-HTAP/pDNA complexes could enter HEK 293A and CHO cells and enabled gene expression at negligible cytotoxicity compared to commercial PEI (20 kDa). These results suggested that bPalm-CS-HTAP can be used as a promising nonviral gene carrier.