Effect of cationic lipid and matrix lipid composition on solid lipid nanoparticle-mediated gene transfer

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 57; no. 2; pp. 155 - 162
• Main Authors: Tabatt, Kerstin, Sameti, Mohammad, Olbrich, Carsten, Müller, Rainer H, Lehr, Claus-Michael
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2004
• Subjects: Animals; Cationic lipids; Cell Survival - drug effects; Cell Survival - genetics; Cercopithecus aethiops; Chemistry, Pharmaceutical; COS Cells; Cytotoxicity; Fatty Acids, Monounsaturated - chemistry; Fatty Acids, Monounsaturated - pharmacology; Lipids - chemistry; Lipids - pharmacology; Matrix lipid; Nanotechnology - methods; Non-viral DNA vectors; Non-viral gene delivery; Quaternary Ammonium Compounds - chemistry; Quaternary Ammonium Compounds - pharmacology; Solid lipid nanoparticles; Transfection - methods; Cytotoxicity; Non-viral DNA vectors; Matrix lipid; Solid lipid nanoparticles; Cationic lipids; Non-viral gene delivery
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2003.10.015

This investigation is focused on the enhancement of in vitro transfection activity by optimizing cationic lipid and matrix lipid composition of solid lipid nanoparticles (SLN). For this purpose SLN were formulated by using two different matrix lipids and six different cationic detergents. These 12 formulations were tested for physical parameters such as particle size, zeta potential and DNA-binding capacity, and also for their biological properties such as cytotoxicity and in vitro transfection efficiency. The SLN were produced by hot high-pressure homogenization, all formulations were physically stable and showed a highly positive surface charge (+34 to +45 mV). In vitro cytotoxicity measurements on COS-1 cells revealed that cytotoxicity is strongly dependent on the cationic lipid used. SLN made from one-tailed cationic detergents were highly cytotoxic. In contrast the two-tailed cationic lipids were all well tolerated. Transfection activity seems to be determined by both the cationic lipid and the matrix lipid used. Here, the combination of cetylpalmitate and N-[1-(2,3-dioleoyloxy)propyl]- N, N, N-trimethylammonium chloride led to significantly higher transfection efficiencies than in all other tested combinations. These results indicate that well tolerated and highly efficient in vitro transfection could be achieved with SLN whenever selecting good combinations of two-tailed cationic lipids and matrix lipids.