While most nucleic acid (NA)-lipid complexes (lipoplexes) are studied in solution, there is growing interest in understanding their properties as naturally derived, biodegradable, biocompatible, solid-state materials with tailorable properties influenced by environmental parameters. Therapeutic applications comprise an important new research field; particularly in gene transfection using plasmid DNA with targeted local delivery for use in cell culture. Nucleic acid-surfactant films are fairly simple to prepare and can be produced on a large scale, depending on the source of DNA or RNA. A DNA-lipid complex is produced by mixing solutions of the nucleic acid and lipid in water, causing a water-insoluble complex to precipitate. The complex is then dried, dissolved in an organic solvent such as isopropanol, and cast on a solid substrate to form a self-standing film via slow solvent evaporation.

However while the films are considered to have promising applications in such diverse fields as drug delivery, photonics, and biocomputation, the structure of the films was a controversial subject in the literature. Furthermore the degradation of such films under biological conditions and in media/serum was not well understood. The structure of a DNA-dimethyldidodecylammonium bromide (DDAB) film in the dry state and in water was investigated by various materials science techniques. We were intrigued to discover that the film could exist in two different structural states and could alternate between these two states rapidly as the film was wetted and dried. The film structure was described further under the influence of humidity and temperature which yielded the discovery of a third structural state. Finally we investigated the application of the films for gene delivery using a luciferase expression assay.

We determined that the films as commonly fabricated are not suitable for biological applications as the DNA and lipid separate from each other in the presence of salt buffer due to charge screening, thus exposing the DNA to degradation by nucleases resulting in low transfection levels. While the films may be further modified to improve their transfection yield we believe that a great deal of further research would be required to achieve this goal.