Needle-Free Transdermal Delivery of mRNA Vaccine with Ionic Liquid Crystals and Effective Tumor Growth Inhibition

Abstract

mRNA vaccines have emerged as a promising therapeutic option based on their ability to elicit a strong immune response, the reduced risk of genomic integration, and the potential to produce various vaccine candidates using the same manufacturing process. However, current mRNA vaccines primarily rely on injection-based administration, which is an invasive procedure that requires a healthcare professional. To address these limitations, transdermal delivery has been proposed as a non-invasive alternative. However, the stratum corneum (SC) acts as a formidable barrier to biopharmaceuticals penetration, necessitating innovative approaches for effective transdermal vaccination. In this study, we developed a novel ionic liquid crystal (ILC), which was formulated from a lyotropic liquid crystal (LLC) using ionic liquids (ILs) with amphiphilic molecular properties. ILC formulations were prepared by mixing ILs with ultrapure water and demonstrated optimal viscoelastic properties for transdermal application. In vitro skin permeation assays revealed the superior mRNA penetration of ILC formulations compared with aqueous mRNA solutions. Furthermore, in vivo evaluation using a tumor-bearing mouse model revealed that transdermal mRNA delivery via ILCs significantly suppressed tumor growth and promoted CD8+ T-cell infiltration into tumor tissues, indicating a potent antitumor effect. These findings highlight the potential of ILC-based transdermal mRNA delivery as a promising strategy for the development of next-generation mRNA vaccine administration methods.