Monday, November 5, 2007 - 10:00 AM
20e

Selective Removal Of Stratum Corneum By In Vivo Microdermabrasion For Transdermal Delivery

Harvinder S. Gill1, Samantha Andrews1, Andrew Fedanov2, Senthil Sakthivel3, Ifor Williams4, David Garber5, Frances Priddy5, Mark Feinberg5, Silvija Staprans6, and Mark R. Prausnitz7. (1) Biomedical Engineering, Chemical and Biomolecular Engineering, Georgia Institute of Technology, 315 Ferst Drive, Atlanta, GA 30332, (2) Emory Vaccine Center, Emory University, Atlanta, GA 30329, (3) Department of Pathology, Emory University, Atlanta, GA 30322, (4) Department of Pathology, Atlanta, GA 30322, (5) Department of Medicine, Division of Infectious Diseases, Emory University, 954 Gatewood Road, Atlanta, GA 30329, (6) Departments of Medicine and Microbiology & Immunology, Emory University, 954 Gatewood Rd., Atlanta, GA 30329, (7) Chemical and Biomolecular Engineering, Biomedical Engineering, Georgia Institute of Technology, 311 Ferst Drive, Atlanta, GA 30332-0100

Transdermal drug delivery is an attractive method for systemic drug delivery. The skin provides a large surface area and a dense vasculature just 0.1 mm deep into the skin. Skin can also be utilized to generate a robust immune response utilizing the skin's protective role orchestrated through epidermal dendritic cells (Langerhans cells), dermal dendritic cells and the epidermal keratinocytes.

Despite the advantages offered by the transdermal route, only a small fraction (i.e., just 16 small and lipophilic molecules from the total compendium of FDA approved drugs) have been effectively delivered across the skin via transdermal patches. The principal cause is the skin's top most layer called the stratum corneum, which provides a formidable transport barrier. This transport barrier can be overcome by removing the stratum corneum in a safe and controlled manner.

Microdermabrasion is an FDA approved method that uses microparticles to abrade the stratum corneum to treat scars and acne. However, in these studies, just partial thickness removal of stratum corneum has been shown. Because a partial removal of the stratum corneum is unlikely to enhance skin permeability for large molecular weight compounds like proteins and DNA, removal of the full thickness of stratum corneum is required for biopharmaceutical and vaccine delivery via the skin.

Motivated to develop microdermabrasion for transdermal drug delivery, we histologically characterized the skin immediately after microdermabrasion in vivo in monkeys and human subjects. Microdermabrasion was performed in both the mobile and the stationary modes, by either moving the microdermabrasion tip on the target skin or by keeping it stationary, respectively. Using the mobile mode on monkeys, the degree of removal of the stratum corneum and epidermis was found to increase with the number of passes. At 50 passes, selective removal of stratum corneum was observed with little damage to the epidermis. Quantitative measurement demonstrated that at 50 passes, greater than or equal to 25% of the skin was devoid of stratum corneum, and only less than 25% of the skin length had epidermis removed. Under the stationary mode, selective stratum corneum removal was not achieved, rather a binary response was observed; either the stratum corneum or epidermis were intact (with or without blisters) or the stratum corneum and epidermis were both removed. Similar removal trends were observed in human subjects under both the mobile and the stationary modes of microdermabrasion.

Finally, delivery of sodium fluorescein and MVA (modified vaccinia Ankara) virus was demonstrated. Biological activity of MVA was also shown through the antibody response. Thus, in this study, we demonstrated for the first time that microdermabrasion can be used to selectively remove the stratum corneum layer and also demonstrated the ability to deliver model hydrophilic compounds and virus through the microdermabraded skin.