Design and formulation of trimethylated chitosan-graft-poly(ɛ-caprolactone) nanoparticles used for gene delivery

Abstract The ideal gene polyplexes should have a subtle balance between polyplex stability to protect DNA against nucleases, and polyplex instability to permit DNA dissociation inside cells. In this research, low molecular weight trimethylated chitosan was chemically modified with poly(ɛ-caprolactone). Owing to the amphiphilic character, trimethylated chitosan-graft-poly(ɛ-caprolactone) (TMC-g-PCL) formed nanoparticles in aqueous media. TMC-g-PCL nanoparticles could effectively condense pDNA into polyplexes about 200 nm in size. The TMC-g-PCL/DNA polyplexes were stable in physiological salt condition and showed high uptake efficiency probably due to the increasing cell membrane-carrier interaction as a result of hydrophobic modification. However, the high degree of quaternization influenced the buffer capacity of TMC-g-PCL and led to a reduction in the release from the lysosomes. By adding chloroquine to exclude the limitation of lysosome escape, the transfection efficiency of TMC-g-PCL/DNA polyplexes was similar to that of PEI/DNA polyplexes. This study demonstrated the potential of TMC-g-PCL/DNA nanoparticles as an efficient carrier for gene delivery.