Structure Optimized Lipid-Based Intradermal Delivery—Needle-Free Transdermal Drug Delivery

Transdermal drug delivery (TDD) exhibits high drug efficacy and minimized side effects over oral administration because it bypasses first hepatic metabolism and gastrointestinal tract. However, the outermost layer of the skin, the stratum corneum (SC; composed of thousands of lipid layers), is recognized as the major barrier in TDD.<br/>With the recent FDA approval case, Microneedle (MN) is recognized as an effective solution for TDD. MN, however, also has an issue with remaining physical damage up to the dermis, where abundant immune cells reside. Therefore, MN can cause external infection and induce the hypersensitivity that can be fatal for children.<br/>Here we devised a needle-free TDD based on lipid as a chemical penetration enhancer. Specifically, we designed structure of lipid nanoparticles with different fusogenicity (liposome &lt; cubosome &lt; hexosome). With structure engineered lipid nanoparticles, Structure Optimized Lipid-based Intradermal Delivery (SOLID) patch was fabricated. Our<i> in vitro</i> test revealed that cubosome- and hexosome-SOLID patch outperforms that of liposome in SC penetration. To understand behind principle of outstanding performance, we conducted <i>in situ</i> synchrotron SAXS study and found out both cubo- and hexo-some show much faster kinetics in SC lipid layer disruption over liposome. Our study indicates that structure engineering of lipid nanoparticle can be an effective approach for the development of needle-free TDD. We believe needle-free TDD can be an effective strategy for not only drug delivery, but many other applications including mRNA intradermal vaccine to prevent pandemic.