Rational design of didodecyldimethylammonium bromide-based nanoassemblies for gene delivery

Nonviral gene vectors are a hot topic for gene delivery. High cost and low transfection efficiency hinder the application of them. The aim of this study was to find out the optimal gene vectors with lower cost and more effective gene delivery than commonly used gene vectors. A cheap cationic lipid, didodecyldimethylammonium bromide (DDAB) was the basic component and the other components included oleic acid (OA), cholesterol (Chol), cholesteryl succinyl poly(ethylene glycol) 1500 (CHS-PEG), poly(D,L-lactide-co-glycolide)-methoxy-poly(ethylene glycol) (PLGA-PEG). The combinations of DDAB/OA/Chol, DDAB/OA/CHS-PEG and DDAB/PLGA-PEG were adopted to prepare the nanoassemblies named CNA, CPNA and PPNA, respectively. The optimal component ratios were screened out according to their Langmuir monolayer behavior. The optimal preparation method of nanoassemblies involved firstly compressing DNA or siRNA with the cationic lipid (DDAB) and secondly being coated with the helper lipids (OA and CHS-PEG) or the helper polymer (PLGA-PEG). The complexes of genes and cationic lipids were encapsulated into the core of CPNA and PPNA. The optimal gene vectors (CPNA and PPNA) with small sizes, low negative surface charges and non-exposure of cationic lipids were achieved. They had the advantages of no cytotoxicity, high transfection efficiency and low cost. More importantly, CPNA and PPNA were not sensitive to serum and showed the similar or higher transfection efficiency of pDNA and siRNA compared to Lipofectamine 2000. CPNA could mainly enter cell plasma based on endocytosis. The rational design method is useful for the design and optimization of DDAB-based gene carriers and other cationic lipid-based carriers.