Biocompatible ionic liquid-based nanoparticles for effective skin penetration and intracellular uptake of antisense oligonucleotides†

Abstract

A novel formulation (IL-NP) for the transdermal delivery of nucleic acid medicines was developed using biocompatible ionic liquid (IL). The formulation was created by mixing DNA in water with an IL in ethanol, followed by freeze-drying and dispersion in oil, producing uniformly sized particles. In vitro studies demonstrated the enhanced skin penetration of IL-NP, while mechanistic studies showed that the IL increased cell membrane fluidity to promote cellular uptake. In vivo experiments with tumor-bearing mice confirmed that transdermal administration of IL-NP achieved comparable antitumor effects as direct injection of DNA, without side effects. This formulation effectively overcomes barriers to both stratum corneum penetration and cellular uptake, providing a non-invasive alternative to injecting nucleic acid therapeutics.