Lyotropic liquid crystal-based transcutaneous peptide delivery system: Evaluation of skin permeability and potential for transcutaneous vaccination

Transcutaneous drug delivery is a promising method in terms of drug repositioning and reformulation be-cause of its non-invasive and easy-to-use features. To overcome the skin barrier, which is the biggest chal-lenge in transcutaneous drug delivery, a number of techniques, such as microemulsion, solid-in-oil dis-persions and liposomes, have been studied extensively. However, the low viscosity of these formulations limits drug retention on the skin and reduces patient acceptability. Although viscosity can be increased by adding a thickening reagent, such an addition often alters formulation nanostructures and drug solu-bility, and importantly, decreases skin permeability. In this study, a gel-like lyotropic liquid crystal (LLC) was used as a tool to enhance skin permeability. In particular, we prepared 1-monolinolein (ML)-based LLCs with different water contents. All LLCs significantly enhanced skin permeation of a peptide drug, an epitope peptide of melanoma, despite their high viscoelasticity. Fourier transform infra-red spectro-scopic analysis of the skin surface treated with the LLCs revealed that the gyroid geometry more strongly interacted with the lamellar structure inside the stratum corneum (SC) than the diamond geometry. Fi-nally, as the result of the in vivo tumor challenge experiment using B16F10 melanoma-bearing mice, the LLC with the gyroid geometry showed stronger vaccine effect against tumor than a subcutaneous injec-tion. Collectively, ML-based LLCs, especially with the gyroid geometry, are a promising strategy to deliver biomacromolecules into skin. Statement of significance Transcutaneous drug delivery is a promising method for drug repositioning and reformulation because of its non-invasive and easy-to-use features. To overcome the skin barrier, which is the biggest challenge in transcutaneous drug delivery, we used a gel-like lyotropic liquid crystal (LLC) as a novel tool to enhance skin permeability. In this paper, we demonstrated that an LLC with a specific liquid crystalline structure has the highest skin permeation enhancement effect for a peptide antigen as a model drug. Moreover, the peptide antigen-loaded LLC showed a vaccine effect that was comparable to a subcutaneous injection in vivo. This study provides a basis for designing a transcutaneous delivery system of peptide drugs with LLC. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Automated summary

Transcutaneous drug delivery is a promising method for drug repositioning and reformulation due to its non-invasive and easy-to-use features. By using a gel-like lyotropic liquid crystal (LLC), this study demonstrated that adjusting the liquid crystalline structure can enhance skin permeation of peptide drugs and show a strong vaccine effect in vivo, providing a basis for designing transcutaneous delivery systems of peptide drugs with LLC.