(557e) Application of the Aqueous Porous Pathway Model to Validate the Ιn Vitro Split-Thickness Skin Model for Ultrasound/Surfactant-Enhanced Transdermal Drug Delivery

Seto, J. E., Massachusetts Institute of Technology
Polat, B. E., Massachusetts Institute of Technology
Blankschtein, D., Massachusetts Institute of Technology
Langer, R., Massachusetts Institute of Technology

The simultaneous application of ultrasound and the surfactant sodium lauryl sulfate (referred to as US/SLS) to skin has been utilized in the clinical setting to enhance the transdermal delivery of low-molecular weight drugs. Current research in this field is focused on optimizing the US/SLS treatment to transdermally deliver therapeutic macromolecules, such as vaccines for transcutaneous immunization (TCI). In TCI, the goal is to deliver the vaccine to the Langerhans cells in the epidermis in order to elicit an immune response. To date, all in vitro research conducted in the field of US/SLS-enhanced transdermal drug delivery (TDD) has been carried out using full-thickness skin (consisting of two layers, the epidermis and the dermis). In order to study the delivery of therapeutic macromolecules into US/SLS-treated skin, to the Langerhans cells or to the blood capillaries at the epidermis-dermis junction, it would be desirable to conduct in vitro US/SLS-enhanced transdermal diffusion experiments using split-thickness skin (STS) models, in which much of the dermis is removed in order to simulate the in vivo transdermal diffusion to the desired skin component. US/SLS treatment enhances TDD in a synergistic mechanical and chemical manner. Since full-thickness skin (FTS) and split-thickness skin (STS) differ in mechanical strength, they may undergo different extents of skin structural perturbation in response to US/SLS treatment. Note that the alternative protocols involving applying US/SLS to FTS and then removing the dermis to create STS are not practically feasible.

In order to validate STS for US/SLS-enhanced TDD studies of hydrophilic permeants, we utilized the aqueous porous pathway model and sucrose (a model hydrophilic permeant) to compare the hydrophilic transport pathways through US/SLS-treated pig FTS (pFTS), 700-μm-thick pig STS (p700), human FTS (hFTS), 700-μm-thick human STS (h700), and 250-μm-thick human STS (h250). Our findings indicate that the extent of structural perturbation of the hydrophilic transport pathways is not significantly different between pFTS, p700, hFTS, and h700, which validates 700-μm-thick STS for US/SLS-enhanced TDD studies of hydrophilic permeants. However, h250 undergoes a greater extent of structural perturbation than the other skin models considered. For hydrophilic macromolecules (including proteins, vaccines, and drug delivery vehicles), p700 may be used because there is less dermis acting as an artificial diffusion barrier in STS compared to FTS, and because excised pig skin is easier to obtain than excised human skin.