TECHNOLOGY & PIPELINE

ETS Terbinafine

Transport’s Electrokinetic Transungual System for onychomycosis consists of an iontophoretic control unit that delivers current to a flexible electrode pre-loaded with a novel formulation of terbinafine. The objective is to drive drug through the nail, as well as to saturate the nail with terbinafine so that the nail acts a drug reservoir, continuing to release terbinafine to the underside of the nail and the nail bed, the sites where the fungi that cause onychomycosis reside. The features of the nail that make drug delivery difficult, lack of blood vessels to deliver drugs and a waxy, impermeant surface, enhance the half-life of drugs that do penetrate. In addition, the internal structure of the nail creates an excellent reservoir for holding drugs and then releasing them slowly over time. While the local concentration of the drug will be high, ensuring rapid and effective treatment, the systemic concentration of the terbinafine will be extremely low, virtually eliminating toxicity and drug interaction concerns.

Transport has conducted in vitro studies to determine if iontophoresis can be used to enhance delivery of terbinafine into and through the nail. These studies were conducted using a modified Franz cell apparatus and, initially, a bovine hoof as a surrogate for human nail. The bovine hoof is a good pre-clinical surrogate for the human nail and provides the advantage of uniform thickness in sliced samples. These studies were able to achieve terbinafine concentrations in the hoof that are 10,000 times greater than the terbinafine concentrations achieved by one month of daily oral Lamisil®. While the hoof is more permeable than the human nail, the data suggests that iontophoresis can significantly enhance the delivery of terbinafine through the nail as represented in the figure below. Pre-clinical studies in human nail are ongoing, and initial data are consistent with that from the hoof model.

Effect of Iontophoresis on Terbinafine Delivery in Bovine Hoof