Research

Skin barrier lipids

Skin barrier lipids consist of an approximately equimolar mixture of ceramides, cholesterol and free fatty acids and form large multimembrane systems in the upper skin layer, the stratum corneum. This unusual composition of high ceramide content is essential for our survival on dry land. Although there is substantial evidence for the role of ceramides in a competent skin barrier and considerable effort has gone into the development of ceramide analogs for the treatment of skin diseases, our understanding of what molecular features of ceramides determine their properties is still limited.

Our long-term aim is to study the structure-activity relationships of skin ceramides to lay the design criteria for a more rational development of ceramide analogs for a potential use in skin disease treatment.

The methods include the synthesis of modified ceramides, investigation of their action in the skin (in vitro using Franz diffusion cells), preparation of model stratum corneum membranes and evaluation of their permeability and lipid biophysics (e.g., infrared spectroscopy, Langmuir monolayers, and, in cooperation, diffferential scanning calorimetry, X-ray diffraction, and atomic force microscopy).

Selected publications:

Transdermal drug delivery and permeation enhancers

2-Akceleranty2.tifTransdermal delivery of drugs to the systemic circulation provides a convenient route of administration. However, the application of this technique to a wider range of drugs is limited due to the remarkable barrier properties of the skin. One of the approaches to increase the number of drugs that can be effectively delivered through the skin is the use of permeation enhancers, also known as penetration/absorption promoters. These chemicals temporarily promote drug flux by interacting with protein or lipid constituents in the skin barrier, the stratum corneum, or by changing the drug partitioning equilibria.

The aim of our work is the design and synthesis of novel chemical enhancers with high activity, low toxicity and reversible action. We also study their mechanisms of action/toxicity in the skin. The selected enhancers are used to increase transdermal flux of selected drugs, namely antivirals and anticancer acyclic nucleoside phosphonates, and vitamin D analogues.

The methods include synthesis of new enhancers, in vitro permeation studies using Franz diffusion cells (porcine skin, human skin), skin electrical impedance, skin microdialysis, tape stripping, and HPLC analysis. In cooperation, we perform cell culture studies and fluorescence microscopy.

Selected publications:

 

 

© 2017 Charles University, Faculty of Pharmacy in Hradec Králové, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech Republic
Website information | Powered by Kentico