Evaluation of the Morphological Effects of TDT 067 (Terbinafine in Transfersome) and Conventional Terbinafine on Dermatophyte Hyphae In Vitro and In Vivo

Abstract

TDT 067 is a novel, carrier-based dosage form of terbinafine in Transfersome (1.5%) formulated for topical delivery of terbinafine to the nail, nail bed, and surrounding tissue. We examined the effects of TDT 067 and conventional terbinafine on the morphology of dermatophytes. Trichophyton rubrum hyphae were exposed to TDT 067 or terbinafine (15 mg/ml) and examined under white light, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Subungual debris from patients treated with TDT 067 in a clinical trial was also examined. Exposure of T. rubrum hyphae to TDT 067 led to rapid and extensive ultrastructural changes. Hyphal distortion was evident as early as 4 h after exposure to TDT 067. After 24 h, there was complete disruption of hyphal structure with few intact hyphae remaining. Exposure to terbinafine resulted in morphological alterations similar to those seen with TDT 067; however, the effects of TDT 067 were more extensive, whereas a portion of hyphae remained intact after 24 h of exposure to terbinafine. Lipid droplets were observed under TEM following 30 min of exposure to TDT 067, which after 24 h had filled the intracellular space. These effects were confirmed in vivo in subungual debris from patients with onychomycosis who received topical treatment with TDT 067. The Transfersome in TDT 067 may potentiate the action of terbinafine by delivering terbinafine more effectively to its site of action inside the fungus. Our in vivo data confirm that TDT 067 can enter fungus in the nail bed of patients with onychomycosis and exert its antifungal effects.

The effect of K101 Nail Solution on Trichophyton rubrum and Candida albicans growth and ultrastructure

“…The later finding, accumulation of lipid droplets was not observed in this study. Use of conventional terbinafine resulted in similar morphological changes, however, not as severe compared with TDT067 …”

“…A study on T. rubrum after treatment with 4‐amino‐3‐methyl‐I‐phenylpyrazolo‐(3,4‐ c ) isothiazole, G8, showed autolytic phenomena and acting by breaking down the endomembrane system including the ‘outer’ membrane . The effect of TDT067, a novel carrier‐based dosage form of terbinafine, on T. rubrum showed extensive ultrastructural changes such as cell collapsing, cell membrane deterioration and disruption of cellular materials and accumulation of lipid droplets . The later finding, accumulation of lipid droplets was not observed in this study.…”

Pharmaceutical liposomal drug delivery: a review of new delivery systems and a look at the regulatory landscape

“…Elastic liposomes have been reported to improve skin penetration of various drugs (Mohammed et al, 2005), and they have been demonstrated for the delivery of drugs such as ibuprofen (Irfan et al, 2012), terbinafine (Ghannouma et al, 2012) and emodin (Lu et al, 2014). Transferosomes have also been reported in clinical studies to varying degrees of success.…”

Hydroxychavicol: A phytochemical targeting cutaneous fungal infections

“…Topical treatment avoids the systemic effects of oral antifungal therapy, and may be preferred by physicians and patients. Topical agents approved for the treatment of mild to moderate fungal nail infection without matrix involvement include formulations based on ciclopirox (a hydroxypiridone) or amorolfine (a morpholine) or terbinafine (an allylamine)14. Ciclopirox, itraconazole, and terbinafine are approved in the United States and around the world for onychomycosis treatment, while amorolfine and fluconazole are approved in Europe9.…”