Abstract
            Purpose: This study evaluated whether a nanostructured lipid carrier (NLC) delivery system  could safely and accurately deliver nucleic acids to the cell nucleus using the enhanced green  fluorescent protein (EGFP)-C1 plasmid model.  
  Methods: The NLC was formulated using the emulsification method and equipped for cationic  lipid-mediated transfection with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), which  interacts electrostatically with nucleic acid. The NLC attributes, including size, polydispersity  index, and zeta potential, were assessed by dynamic light scattering (DLS). The morphological  structure was analyzed using transmission electron microscopy. Entrapment efficiency was  evaluated by a direct method. Cellular uptake mechanisms of pEGFP-C1-NLC and the ability of  pEGFP-C1 to penetrate the nucleus of TM4 cells to express EGFP were observed using confocal  microscopy.  
  Results: pEGFP-C1-NLC exhibited particle sizes in the range 56-88 nm with a particle charge  range of -6.0 to+1.3 mV. The polydispersity index<0.5 showed good size uniformity, and  entrapment efficiency of pEGFP-C1in the NLC was 92.06±2.295%. The NLC formulation was  internalized predominantly via caveolae-mediated endocytosis, as indicated by EGFP expression  following successful delivery of pEGFP by the NLC into the cells.  
  Conclusion: NLC formulation could deliver genetic material to the nucleus and could be  considered a gene therapy candidate for spermatogenesis.