Pedersen Nina, Hansen Susan, Heydenreich Annette V, Kristensen Henning G, Poulsen Hans S
Department of Radiation Biology, Finsen Center, National University Hospital, Copenhagen, Denmark.
Eur J Pharm Biopharm. 2006 Feb;62(2):155-62. doi: 10.1016/j.ejpb.2005.09.003. Epub 2005 Nov 14.
Cationic solid lipid nanoparticles (SLN) have recently been suggested for non-viral gene delivery, as these particles consist of well tolerated substances, can bind DNA directly via electrostatic interactions and mediate gene transfer in vitro. We here report the development of SLN complexes, which can be targeted to specific surface receptors. A formulation of SLN was prepared by the microemulsion technique comprising of stearylamine and the matrix lipid Compritol ATO 888 with a size of approximately 100 nm and a zeta-potential of +15. These SLN are able to condense DNA in complexes, which are very stable under physiological conditions, and they display low cytotoxicity in cell culture. In addition to binding of DNA, the SLN can simultaneously bind substantial amounts of streptavidin directly via electrostatic interactions. The SLN:DNA: streptavidin complexes are stable and are capable of binding biotinylated ligands, which can interact with surface receptors. This method allows for development of a fast and simple method of preparing a targeted non-viral gene therapy vector.
阳离子固体脂质纳米粒(SLN)最近被提议用于非病毒基因递送,因为这些颗粒由耐受性良好的物质组成,可通过静电相互作用直接结合DNA并在体外介导基因转移。我们在此报告了可靶向特定表面受体的SLN复合物的开发。通过微乳液技术制备了一种SLN制剂,其由硬脂胺和基质脂质Compritol ATO 888组成,尺寸约为100 nm,ζ电位为+15。这些SLN能够在复合物中浓缩DNA,该复合物在生理条件下非常稳定,并且在细胞培养中显示出低细胞毒性。除了结合DNA外,SLN还可以通过静电相互作用同时直接结合大量链霉亲和素。SLN:DNA:链霉亲和素复合物是稳定的,并且能够结合可与表面受体相互作用的生物素化配体。该方法允许开发一种快速简单的制备靶向非病毒基因治疗载体的方法。