Research teams led by Professor Oh Seung-su of the Department of Materials Science and Engineering at Pohang University of Science and Technology POSTECH and Professor Choi Si-young of the Department of Chemical and Biomolecular Engineering at KAIST said on the 28th that they identified the molecular structures of fatty acids that determine the efficiency of drug delivery through the skin. The findings were published in July in the international journal Chemical Engineering Journal.
Drug delivery through the skin is simpler than injections, but the stratum corneum, the outermost layer of the skin, blocks penetration of external substances, limiting its application. In particular, drugs that dissolve well in water, such as insulin or peptides, have difficulty passing through the skin barrier where lipid components are tightly packed.
The researchers focused on free fatty acids among penetration enhancers that loosen the skin barrier. They applied 24 fatty acids with different carbon chain lengths and double-bond positions to artificial skin and pig skin, and analyzed their arrangements within the lipid layer through molecular dynamics simulations.
As a result, disrupting the skin lipid structure more did not necessarily increase drug permeability. Instead, the molecular shape of fatty acids and their orientation within the lipid layer emerged as more important factors.
In particular, fatty acids with 18 carbon atoms and a cis double bond in the middle of the chain, which kinks the molecular structure, were effective at improving skin penetration of hydrophilic drugs. The researchers analyzed that this structure lowers the energy barrier required for drugs to pass through the skin.
The team also developed a "photo-switchable fatty acid" whose molecular structure changes upon light exposure. Experiments showed that the degree of skin penetration of drugs varied with light-induced structural changes in the fatty acid.
Professor Oh Seung-su said, "We confirmed the relationship between the molecular structure of fatty acids and skin penetration," and added, "This can be extended to various biomembranes and stimulus-responsive drug delivery technologies going forward."
References
Chemical Engineering Journal (2026), DOI: https://doi.org/10.1016/j.cej.2026.179663