Framework nucleic acids (FNAs) are emerging nanocarriers owing to their inherent biocompatibility, precise assembly, and inherent compatibility with NA therapeutics. Topical administration of FNAs promises gene therapy of skin diseases. However, their stabilization and delivery efficiency across the stratum corneum remain a challenge. This work reports the use of choline carboxylic acid-based ionic liquids to simultaneously address these two hurdles. First, the FNAs are assembled and solvated, and their structural stability is confirmed using fluorescence spectroscopy, dynamic light scattering, and gel electrophoresis. Of the six formulations tested, choline octenoate exhibits the best stabilizing properties at room temperature. Additionally, this formulation successfully transports FNAs into the lower dermis region in intact, ex vivo porcine skin.
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