Effect of cationic lipid and matrix lipid composition on solid lipid nanoparticle-mediated gene transfer.
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.
Tabatt
Kerstin
K
Department of Pharmaceutical Technology, Biopharmacy and Biotechnology, Freie Universität, Berlin, Germany.
Sameti
Mohammad
M
Olbrich
Carsten
C
Müller
Rainer H
RH
Lehr
Claus-Michael
CM
D000818:Animals; D019556:COS Cells; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002626:Chemistry, Pharmaceutical; D002522:Chlorocebus aethiops; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry* / Q000494:pharmacology*; D008055:Lipids / Q000737:chemistry / Q000494:pharmacology; D036103:Nanotechnology / Q000379:methods*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry* / Q000494:pharmacology*; D014162:Transfection / Q000379:methods*
D005229:Fatty Acids, Monounsaturated; D008055:Lipids; D000644:Quaternary Ammonium Compounds; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane