Novel cationic SLN containing a synthesized single-tailed lipid as a modifier for genedelivery

Abstract

Cationic solid lipid nanoparticles (SLN) can bind DNA directly via ionic interaction andmediate in vitro gene transfection. However, toxicity is still an obstacle, which is stronglydependent on the cationic lipid used. In the present study, a novel single-tailed cationiclipid, 6-lauroxyhexyl lysinate (LHLN), was synthesized and used as a modifier to preparestable SLN–DNA complexes by a nanoprecipitation method. The commonly usedcationic lipid cetyltrimethylammonium bromide (CTAB) modified SLN–DNAformulation served as a contrast. These two formulations were characterized andcompared in terms of morphology, particle size, surface charge, DNA binding capacity,release profile, cytotoxicity, and transfection efficiency. The LHLN SLN–DNAcomplexes had a similar spherical morphology, a relatively narrow particle sizedistribution and a more remarkable DNA loading capability compared to theCTAB ones. Most importantly, LHLN modified SLN had a higher gene transfectionefficiency than the naked DNA and CTAB ones, which was approximately equalto that of Lipofectamine–DNA complexes, and a lower cytotoxicity comparedwith CTAB–SLN and Lipofectamine 2000. Thus, the novel cationic SLN canachieve efficient transfection of plasmid DNA, and to some extent reduce thecytotoxicity, which might overcome some drawbacks of the conventional cationicnanocarriers in vivo and may become a promising non-viral gene therapy vector.