NB-002, a Novel Nanoemulsion with Broad Antifungal Activity against Dermatophytes, Other Filamentous Fungi, and Candida albicans

Abstract

NB-002 is an oil-in-water emulsion designed for use for the treatment of skin, hair, and nail infections. The activity of NB-002 was compared to the activities of the available antifungal drugs against the major dermatophytes responsible for cutaneous infections, Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum, and Microsporum spp., as well as 12 other genera of filamentous fungi. NB-002 consistently displayed fungicidal activity against all dermatophytes. The comparator compounds were either fungistatic or fungicidal, and for some strain-drug combinations, tolerance was observed. Assessment of the development of spontaneous resistance to NB-002 in different dermatophyte species yielded few stably resistant mutants. For filamentous nondermatophyte fungi, the MIC range varied from 0.06 to 0.5 g/ml for Alternaria spp. to 2 to 8 g/ml for Paecilomyes spp. NB-002 had activity against both azole-susceptible and -resistant Candida albicans yeast isolates, with MIC 90 s of 2 g/ml, respectively, and minimum fungicidal concentrations at which 90% of isolates are inhibited of 4 and 8 g/ml, respectively. The kinetics of the fungicidal activity of NB-002 against T. rubrum isolates were compared to those of the other antifungal drugs. NB-002 killed both mycelia and microconidia even when the fungal forms were dormant or not actively growing. Electron micrographs of mycelia and spores treated with NB-002 showed the significant disruption of the fungal structure. The in vitro broad coverage of NB-002 against filamentous fungi, dermatophytes, and C. albicans, as well as its rapid fungicidal activity, warrants further investigations to ascertain if NB-002 would be useful for the treatment of cutaneous mycoses.Superficial fungal infections are found in the top layers of the skin and mucous membranes, the hair, and nails. Examples of fungal infections of the skin and other external surfaces include athlete's foot, jock itch, ringworm, and other tinea infections. Most of these infections are caused by three genera of dermatophytes: Trichophyton, Epidermophyton, and Microsporum spp. (3,4,20,29,45,47).Filamentous fungi that are normal soil saprophytes have also emerged as major opportunistic fungi, especially in immunosuppressed patients (34,53). Such organisms include Aspergillus spp.

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