DNA Interactions with Functionalized Emulsions

Authors

Thierry Delair CNRS-bioMérieux, École Normale Supérieure de Lyon

Publication Date

4/20/04

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Abstract

Synthetic colloidal DNA carriers have been under intense investigation lately as they represent one of the safer alternatives to viral-mediated gene delivery. Moreover, in vaccination purposes, the group of Singh has demonstrated that DNA adsorbed onto particle surface could be a potent immunogene. Colloidal carriers include particles, i.e., hard spherical objects made from polymers, and emulsions, dispersions of a liquid nonsoluble in the continuous phase, which most of the time are “soft objects.” Depending on the size of the droplets, the emulsions will be named macro-, micro-, or nanoemulsions. Emulsions are thermodynamically unstable, except for micro- or nanoemulsions, which can form spontaneously, upon mixing the appropriate amounts of components, in particular with a high concentration of surfactants. Emulsions are oil-in-water (O/W) dispersions or the reverse (water-in-oil, W/O) very often stabilized with phospholipids as surface active agent. They structurally differ from liposomes which consist in phospholipidic bilayers (ideally one) surrounding an aqueous core.

In clinics, emulsions have long been used for parenteral nutrition and later for drug delivery, as a means to reduce the toxicity of the active substance. So, a solid technical background exists for the production at high scale and low cost of safe carriers for in vivo applications. Moreover, compared to related DNA particulate vectors, the manufacture of emulsions does not require the use of solvents, and components are well tolerated by the body, as for instance lipids such as triglycerides or olive oil, etc.

For DNA delivery, nanotechnologies are expected to develop formulations of nanocomposites capable of interactions with nucleic acids and transport to the targeted site. The nanometer-size range of these carriers allows a better uptake by cells and even offers the capability to cross the blood–brain barrier. Moreover, nanoparticles can be administrated into the systemic circulation with no risk of aggregation and blockage of fine blood capillaries. In some applications, it may be essential to target not only a tissue, but as well a specific compartment of the cells. Hence this chapter will be devoted to the elaboration of nanosized emulsions, their interactions with DNA, and various applications of these composite objects.