br Introduction Superficial mycoses have

Introduction Superficial mycoses have an increasing incidence rate, with 20–25% of the world population being affected. The main reasons attributed to the rise in these infection rates include migration, tourism, and socioeconomic conditions. These infections are mainly caused by dermatophytes (pathogenic keratin-digesting fungi) belonging to the genera Epidermophyton, Microsporum, and Trichophyton. Commonly, dermatophytes are limited to superficial skin, hair, and nails, causing disfiguring and discomfort. The soles and toe webs of feet are the most frequently affected sites in tinea pedis infection. Common clinical manifestations include intertriginous dermatitis presented with maceration, peeling, and fissuring in toe interspaces. Trichophyton mentagrophytes causes an acute inflammatory condition characterized by the formation of pustules, vesicles, and sometimes bullae. Tinea pedis is generally treated with topical application of different antifungal agents in the form of creams, gels, sprays, liquids, and powders. Topical terbinafine has been widely applied for the treatment of tinea pedis. Terbinafine is a fungicidal allylamine compound with an excellent safety profile. It inhibits the synthesis of ergosterol, an important fungal cell membrane and GSK2126458 component. Although different topical formulations of terbinafine are available on the market, effective drug delivery to the target site has still not been achieved. The main problem with conventional topical formulations is the easy removal of formulation from the site of application, leading to insufficient amounts of drug reaching the site of action. Different strategies can be adopted to enhance skin permeation, including preparation of bioadhesive formulations or increasing lipid bilayer permeability by hydration techniques. In this study, film-forming gel containing terbinafine was prepared to enhance terbinafine permeation by affecting lipid bilayer permeability through hydration. Chitosan is a natural, cationic, hydrophilic biopolymer that interacts with the negatively charged skin surface, conferring enhanced bioadhesiveness and percutaneous penetration. In this study, a film-forming gel of terbinafine (DA5505) was prepared using chitosan for effective delivery of terbinafine in a guinea pig model of tinea pedis.
Methods
Results
Discussion Differences in terbenafine skin permeation were observed, following application of different formulations. Important factors affecting drug absorption and skin penetration include the film-forming agent and the solvent. Use of chitosan as a film-forming agent in DA5505 possibly assisted the enhanced skin permeation of terbinafine. Chitosan can significantly change the secondary structure of keratin present in stratum corneum, and enhance the water content and cell membrane fluidity to different degrees, leading to improved skin permeation. In addition, ethanol present in the formulation could lead to enhanced skin penetration. Aqueous alcoholic solutions extract lipids and proteins from the skin, minimizing skin barrier functions and rendering the membrane more permeable. Skin retention of pharmaceuticals plays a vital role in the treatment of topical infections. In fungal infections, the efficacy of therapy is based on the amount of the antifungal drug reaching and residing at the site of infection. Results from our study revealed that DA5505 exhibited higher porcine skin retention than the marketed solution, gel, and cream formulations. As explained previously, film-formers are present in the formulation. During the process of film formation, if the solubility of the drug is exceeded, crystallization occurs, resulting in limited skin permeation. Therefore, terbinafine crystallization could have led to limited drug permeation and retention by Lamisil Once, compared with DA5505. Gel and cream formulations could not sufficiently interact with the skin, leading to lower terbinafine retention.