ABSTRACT
Naftifine is used to treat fungal skin infections as it inhibits dermatophytes, which are the cause of onychomycosis. However, naftifine's ability to permeate the human nail barrier has not been investigated, thus, the antimycotic potential is not clearly established. This work aims to evaluate the effect of penetration enhancing factors on the accumulation of naftifine hydrochloride through human nail clippings. Naftifine polymeric nail lacquers with Eudragit RL100 were developed as a suitable delivery system. Low penetration of naftifine into nail has been determined as less than 10% of applied drug dose accumulated in the nail layers. Incorporation of thioglycolic acid into formulations resulted in increased accumulation of antifungal agent in the nail layers by 100% compared with a control group. Salicylic acid did not effect naftifine accumulation in the human nail. The permeation of naftifine through the nail increased by threefold when the thioglycolic acid-containing formulation was applied and the nail was pretreated with a fractional CO2 laser. Structural changes of the nail barrier, induced by fractional CO2 laser, were visualized by microscopy. The results suggest, that naftifine nail penetration could be significantly increased when physical and chemical enhancing factors are applied.
Subject(s)
Allylamine/analogs & derivatives , Antifungal Agents/administration & dosage , Drug Delivery Systems , Hoof and Claw/drug effects , Nails/drug effects , Onychomycosis/drug therapy , Administration, Topical , Adult , Allylamine/administration & dosage , Allylamine/pharmacokinetics , Animals , Antifungal Agents/pharmacokinetics , Cattle , Female , Hoof and Claw/metabolism , Humans , Lacquer , Male , Middle Aged , Nails/metabolism , Onychomycosis/metabolism , Tissue DistributionABSTRACT
Topical monotherapy of nail infection is limited by poor drug permeability into the human nail plate. Numerous substances and methods are applied to improve the antifungal agent delivery across the nail plate. This work aimed to evaluate the effect of chemical and physical enhancers on the accumulation and permeation of amorolfine hydrochloride through human nail clippings. Polymeric nail lacquers with Eudragit E100 were developed as a potentially suitable delivery system for amorolfine hydrochloride. Incorporating thioglycolic acid and urea into formulations provided increased accumulation of antifungal agent in nail layers of up to 100% and 57%, respectively. Structural changes of nail barrier, induced by fractional CO2 laser, were visualized by microscopy. The permeation of amorolfine hydrochloride through the nail increased twofold when thioglycolic acid-containing formulation was applied and the nail was pretreated with a fractional CO2 laser. The results suggest that this novel combination of enhancers has the potential to be an effective option for topical drug delivery through the nail, and increased the efficacy of treatment.
