Thin films and coatings that promote the contact-transfer of nucleic acids to cells and tissues have the potential to be useful in a broad range of biomedical and biotechnological contexts. Contact-mediated delivery often requires quick release of DNA or the rapid separation of a coating from its underlying substrate (e.g., over periods of seconds or minutes), but many polymer films fall apart or release DNA on much slower time scales (e.g., over many hours, days, or weeks) and are thus not useful for such applications. Here, we report a strategy for the design of thin polyelectrolyte-based multilayer coatings that enables the ‘quick release’ and rapid contact-transfer of plasmid DNA to other secondary surfaces in as little as 30 seconds when pressed into contact with tissue or other soft objects. This approach is based on the incorporation of layers of weak polyelectrolytes such as poly(acrylic acid) (PAA) into polyelectrolyte multilayers fabricated using layer-by-layer assembly. We demonstrate that this approach can be used to promote the rapid disassembly and contact transfer of DNA-containing films fabricated using a range of different degradable and non-degradable polyamines, through a mechanism that involves the ionization of PAA at physiological pH. This approach thus enables contact-transfer of DNA to objects surrounded by or bathed in physiological media. We demonstrate that this approach can be used to coat the surfaces of inflatable catheter balloons and used to promote the inflation-induced contact-transfer of plasmid DNA to the peripheral arteries of pigs as well as other soft, deformable objects, including hydrogels with planar or curved geometries. Aspects of film fabrication, polymer structure, environmental conditions, and physical forces and parameters that influence rates and extents of film transfer will be discussed. These new quick-release materials enable rapid, contact-transfer of DNA and potentially other biomolecular agents, and thus open the door to the design of new therapeutic strategies, including microneedle and angioplasty balloon-based therapies, that would be difficult to achieve using conventional polymer-based materials. Advances toward potential applications and new approaches to promoting the rapid release of DNA-containing coatings based on the design of rapidly dissolving hydrogen-bonded sacrificial layers will also be presented.

Incorporation of a weak poly(acid) into multilayer polymer coatings enables rapid contact-transfer of DNA to soft surfaces

255th National Meeting (2018)

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