Enhanced skin permeability for transdermal drug delivery: physiopathological and physicochemical considerations

To deliver drugs through the skin for systemic medication, the skin permeability needs enhancing by either modifying the drug molecules, or applying skin permeation enhancers to reduce the barrier property of the skin. Traditionally, the enhancement of skin permeability is considered as the result from the improvement of the lipophilicity of drugs and the partition of drugs into the skin, or from the direct actions of skin permeation enhancers on the chemical structure and/or composition of lipids and proteins in the stratum corneum. However, on the other hand, the skin also responds to drugs and/or skin permeation enhancers physiopathologically via its inflammatory and immune reaction. The physiopathological responses of the skin can also induce the changes in the chemical structure and composition of lipids and proteins in the skin. Therefore, the possible role of physiopathological responses of the skin in the enhanced skin permeability should be concerned.