Self-assembled nanoparticles from bis-palmitoylated and quaternized chitosan: promising materials for gene delivery

We have developed a preparative procedure for obtaining a bis-palmitoylated and quaternized chitosan (bisPalm-CS-HTAP) bearing N-(2-((2,3-bis(palmitoyloxy) propyl) amino)-2-oxoethyl) (bisPalm) groups as hydrophobic tails and O-[(2-hydroxyl-3-trimethylammonium)] propyl (HTAP) groups as positively charged hydrophilic heads. The product obtained showed the degree of bis-palmitoyl substitution (DS_bisPalm) and the degree of quaternization (DQ) at approximately 2 % and 50 % as determined by solid-state ¹³C NMR and ¹H NMR respectively. As characterized by SEM, bisPalm-CS-HTAP was found to assemble into spherical nanoparticles. The hydrodynamic diameter (D_H) and the surface charge of the nanoparticles, as analyzed by DLS, were about 260 nm (PdI = 0.5) and 40 mV respectively, demonstrating the arrangement of the positively charged HTAP groups on the outer layer of the assembly. These positively charged and nanosized particles possess a strong potential to be used as a carrier for gene delivery. More inportantly, the built-in bis-palmitoyl groups would allow for membrane attachment of the material, resulting in the enhancement of cellular uptake.