학술논문

Effect of Hydrophilic Chain Length in Non-Ionic Surfactant on the Physicochemical Characteristics, Gene Expression Efficiency and Cytotoxicity of DNA/Poly-L-Ornithine/Niosome Ternary Complexes for Gene Delivery
Document Type
Journal Article
Source
Journal of Pharmaceutical Science and Technology, Japan. 2020, 80(3):156
Subject
gene delivery
niosomes
non-ionic surfactant (NIS)
poly-L-ornithine (PLO)
polyoxyethylene stearyl ether (steareth)
Language
English
ISSN
0372-7629
2188-3149
Abstract
The aim of this study is to clarify the effect of hydrophilic ethylene oxide (EO) chain length in steareths on the physicochemical characteristics, gene expression efficiency and cytotoxicity of plasmid DNA (pDNA)/poly-L-ornithine (PLO)/niosomes (consisting of non-ionic surfactants [NISs], polyoxyethylene stearyl ethers [steareths]) ternary complexes. Niosomes were prepared with NISs, a series of steareth (steareth-2, steareth-5 and steareth-20) or Tween 80, cholesterol, and octadecylamine of cationic lipid, followed by complexing with pDNA encoding luciferase gene and PLO. The physicochemical characteristics, gene expression efficiency and cytotoxicity of the prepared pDNA/PLO/niosome ternary complexes were evaluated. The particle size and ζ potential of steareth niosomes and pDNA/PLO/steareth niosome ternary complexes decreased with lengthening of the EO chain in steareth. All complexes showed a high pDNA condensation ability, and pDNA/PLO/steareth-2 niosome ternary complexes possessed the highest protective effect in the presence of polyanion, dextran sulfate. The transfection efficiency and cell viability of pDNA/PLO/steareth niosome ternary complexes also decreased with the lengthening of the EO chain. Among the pDNA/PLO/niosome ternary complexes, the pDNA/PLO/steareth-2 niosome ternary complexes showed the highest transfection efficiency and almost no cell damage. In conclusion, it was suggested that the EO chain length in steareths affects the physicochemical characteristics, gene expression efficiency and cytotoxicity of pDNA/PLO/steareth niosome ternary complexes. Furthermore, we pointed out that the pDNA/PLO/steareth-2 niosome ternary complexes might deliver genes efficiently and safely. Further study is required to more elevate the transfection efficiency, stability and safety of pDNA/PLO/steareth-2 niosome ternary complexes, such as using target compounds.