The Challenge of Nucleic Acid-Surfactant Films for Transfection

Synthetic transfection vectors have tremendous potential as non-viral transfection reagents, allowing for ease of preparation and avoiding the immunogenic and mutational concerns associated with viral vectors.  These vectors are typically formed via electrostatic complexation of negatively-charged nucleic acids with positively charged polymers (polyplexes) or surfactants (lipoplexes).  While initial studies focused on the bolus delivery of these complexes as nanoparticles in solution, there are a large number of applications that would benefit from a more localized transfection strategy, such as thin films or surface-mediated delivery. 

Thin films and surface mediated delivery has the potential to enable higher transfection efficiencies compared to solution-based methods.  By localizing the transfection reagents onto a surface, cells in contact with this surface will experience a more consistent and higher local concentration of the transfection reagent than in the case of bolus delivery.  Furthermore, layered films have the potential to provide both controlled release of transfection reagents over time, or sequential release of various factors for more complex experiments.  While a variety of strategies for surface-mediated delivery have been reported, the vast majority have utilized polyplexes, ^1-4 there have been very few reports of lipoplex-based films.^5-7

The main difference between surfactant and polymer based transfection complexes lies in the monovalent vs. multivalent interaction of surfactants as compared to polymers.  In fact, lipoplexes have often performed better than polyplexes because the weaker monovalent interactions between the surfactants and nucleic acids helps to facilitate release of the genetic material upon delivery to the nucleus while polyplexes must often be designed specifically to degrade.  However, these weaker interactions have also resulted in significant challenges in attempting to develop thin film-based methods for lipoplex delivery.  Here we examine these challenges in detail and present suggestions for future efforts associated with surface-mediated surfactant-based therapies.

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