N-hexanoyl, N-octanoyl and N-decanoyl chitosans: Binding affinity, cell uptake, and transfection.

Low transfection efficiency of chitosan limits its use as a non-viral vector for practical purposes. This study was designed to investigate the effect of fatty acyl chain length on physicochemical properties, pDNA binding affinity, cell uptake, and in vitro transfection efficiency of N-acyl chitosan (NAC). NAC polymers were synthesized by carbodiimide mediated coupling reaction of chitosan with n-hexanoic, n-octanoic, and n-decanoic acid, respectively. These NAC polymers effectively condensed pDNA resulting in the size range of 220-342 nm with net positive charge. NAC polymers also showed good pDNA binding capacity, high protection of pDNA from nuclease degradation and excellent biocompatibility. Transfection efficiency of chitosan, in HEK 293 cells, was enhanced 15-25-fold after coupling with fatty acid and increased with a decrease in fatty acyl chain length of NAC. Thus, the present study demonstrates that the NAC polymers hold great potential as novel non-viral gene delivery vector.