Transungual (Nail) Drug Delivery

With foregoing successful years in topical and transdermal delivery, the Center for Dermal Research is now expanding its focus towards another challenging field of delivery: nail (transungual) drug delivery. Transungal local delivery is desirable when treating nail diseases due to localized effects with minimum systemic side effects. However, the effectiveness of topical therapies is limited by low drug permeability through the highly keratinized compact nail plate.

There are different approaches to nail delivery which include chemical means of increasing penetration through nails, physical means and electrochemical. Approximately, one half of all nail conditions are the result of fungus, making onychomycosis one of the most common nail disorders. Onychomycosis affects approximately 35 million Americans and currently 85% of these patients are untreated since currently prescribed oral anti-fungal medicines cause serious side effects such as liver damage. Therefore, there is significant need for effective local drug delivery through nails for treatment of onychomycosis and other nail disorders such as nail psoriasis, yellow nail syndrome, paronychia, pitting of nails and hyperkeratosis. The Center for Dermal Research is well equipped for formulation design, development and transungual permeation studies and has access to facilities for microscopic examination (e.g. confocal microscopy and spectroscopic imaging of the nail plate). We are now focusing on novel approaches for enhanced nail delivery for efficient treatment of nail disorders and evaluating their perungual drug absorption following topical application.

Transungual drug delivery refers to the drug transport across the nails to achieve targeted drug delivery for treatment of nail diseases. Onychomycosis is a fungal disease of the nail that is growing rapidly worldwide especially in the older population. The condition involves discoloration, brittleness and thickening of the nails. It is a recurring disease seen more in toenails than in fingernails and the challenge is to achieve effective drug delivery topically rather than by the oral route, the latter posing greater risks of systemic adverse effects. A transungual drug transport system provides a better delivery route than oral or systemic treatment of fungal infections due to its better adherence, localized action and minimum systemic side effects . Transungual drug delivery studies at the Center for Dermal Research have been expanded significantly with interest in deep nail layer delivery. We are working with novel formulations containing different anti-fungal drugs to achieve effective delivery. After establishing initial analytical characterization of anti-fungal drugs and human cadaver nails, we have begun permeation studies using modified Franz Diffusion Cells with nail adapters.

(Figure 7, Figure 8)

Efforts are being made not only towards achieving drug permeation through the nail, but also understanding lateral diffusion of drugs in the nail layers. We have collaborations with our partners at TRI Princeton and other research groups with the latest technology platforms and testing capabilities to enhance our efforts in this area. Currently, we are focusing on developing different formulation strategies with potential antifungal molecules such as terbinafine hydrochloride, econozaole, ketoconazole, and others to target the disease and achieve effective antifungal therapies. We are exploring various formulations such as microemulsion/nanoemulsion gels, lipid nanostructures and nail lacquers for treating fungal infections

(Figure 4).
Figure 8: Franz diffusion cell with nail adapters
Figure 7: