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 because of its non-invasive and easy-to-use features. To overcome the skin barrier, which is the biggest challenge in transcutaneous drug delivery, a number of techniques, such as microemulsion, solid-in-oil dispersions 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 solubility, 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 spectroscopic 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. Finally, 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 injection. 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.

[The effect of the external biliary diversion on cobalamin functions].

We studied the effect of the external biliary diversion on cobalamin functions clinically and experimentally. Serum cobalamin was rising to 10 ng/ml or more in each patient with obstructive jaundice and the diverted bile contained high concentrations of cobalamin (10-80 ng/ml). A total volume of diverted cobalamin reached to 2-12 micrograms/day after the relief of obstruction and was maintained 2-8 micrograms/day even after 30 days. In experimental dogs, serum cobalamin decreased to 360 +/- 40pg/ml (about 31% decreases) subsequent eight weeks after the relief. The cobalamin concentration of liver decreased to 184 +/- 123ng/g (19% decreases) after four weeks and to 164 +/- 108ng/g (30% decreases) after eight weeks. The concentration of the different cobalamins in the liver showed that the proportion of dimethyl benzimidazolyl cobamide coenzyme (DBCC) decreased and the proportion of methylcobalamin increased. It is concluded that cobalamin (10 micrograms/day at least) should be administered when the diversion continues for a long term.