Abstract

Cationic solid lipid nanoparticles (SLN) for gene transfer are formulated using the same cationic lipids as for liposomal transfection agents. To investigate the differences and similarities in structure and performance between SLN and liposomes, a SLN preparation (S1), its counterpart formulation without matrix lipid (L1), a commercially available liposomal preparation (DLTR) — all based on the cationic lipid DOTAP—and a liposomal formulation that additionally contained the helper lipid dioleoylphosphatidylethanolamine (DOPE) (Escort™) were compared. Photon correlation spectroscopy (PCS) showed that the SLN were smaller in diameter than the corresponding liposomes (88 vs. 148 nm) and atomic force microscopy (AFM) supported the expected structural differences. Desoxy ribonuclein acid (DNA) binding differed only marginally. Surprisingly, reporter gene expression was comparable between all DOTAP based formulations (S1, L1, DLTR), surpassed only by the DOPE containing liposomes (Escort™). In conclusion, cationic lipid composition seems to be more dominant for in vitro transfection performance than the kind of colloidal structure it is arranged in. Hence, cationic SLN extend the range of highly potent non-viral transfection agents by one with favourable and distinct technological properties. Further SLN optimisation should be facilitated by the accumulated knowledge about cationic lipids in liposomal formulations.

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