Formulation of Tioconazole and Melaleuca alternifolia Essential Oil Pickering Emulsions for Onychomycosis Topical Treatment

Abstract

Onychomycosis is a disease that affects many adults, whose treatment includes both oral and topical therapies with low cure rates. The topical therapy is less effective but causes fewer side effects. This is why the development of an effective, easy to apply formulation for topical treatment is of high importance. We have used a nanotechnological approach to formulate Pickering emulsions (PEs) with well-defined properties to achieve site-specific delivery for antifungal drug combination of tioconazole and Melaleuca alternifolia essential oil. Silica nanoparticles with tailored size and partially hydrophobic surface have been synthesized and used for the stabilization of PEs. In vitro diffusion studies have been performed to evaluate the drug delivery properties of PEs. Ethanolic solution (ES) and conventional emulsions (CE) have been used as reference drug formulations. The examination of the antifungal effect of PEs has been performed on Candida albicans and Trichophyton rubrum as main pathogens. In vitro microbiological experimental results suggest that PEs are better candidates for onychomycosis topical treatment than CE or ES of the examined drugs. The used drugs have shown a significant synergistic effect, and the combination with an effective drug delivery system can result in a promising drug form for the topical treatment of onychomycosis.

Antifungal Combinations in Dermatophytes

“…Combination included: azoles or terbinafine or griseofulvin plus plant extracts including essential oils (19/30 studies), azoles or terbinafine or amorolfine plus immunosuppressant agents (3 studies), azoles or terbinafine plus peptides (3 studies), azoles plus disinfectants (3 studies), and other combinations including antifungal agents plus efflux pump inhibitors and statins. Checkerboard titration methodology was the most common procedure for testing the combination, followed by agar methods (i.e., disk diffusion and agar dilution) [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ].…”

“…They act in two ways: by neutralizing free radicals (the antioxidant effect) and as anti-inflammatory agents by inhibiting the release of pro-inflammatory mediators. Secondary metabolites produced by plants are also capable of acting in a third way, as antifungal agents [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ]. A synergistic interaction between antifungal agents and natural products was often seen ( Table 2 ).…”

“…A synergistic interaction between antifungal agents and natural products was often seen ( Table 2 ). One recent study evaluated the antifungal activity of tea tree oil (TTO) ( Melaleuca alternifolia essential oil) and its main components against T. rubrum alone and in association with ketoconazole or itraconazole and showed either their fungicidal effects or a synergism upon combination with azoles [ 49 ]. Most of the studies demonstrated that the type of interaction was either isolate- or drug-dependent.…”

Antifungal Properties of Essential Oils and Their Compounds for Application in Skin Fungal Infections: Conventional and Nonconventional Approaches

“…For this purpose, a nanotechnological approach was applied to formulate PEs in combination with azole derivative (tioconazole) and Melaleuca alternifolia EO tested against C. albicans and T. rubrum . The findings showed that PEs are an excellent choice for onychomycosis topical treatment compared to conventional emulsions or ethanolic solutions of reference drugs [ 145 ].…”

Constant Voltage Iontophoresis Technique to Deliver Terbinafine via Transungual Delivery System: Formulation Optimization Using Box–Behnken Design and In Vitro Evaluation

“…Briefly, 30 mL of sterile SDA was added in one Petri dish (90 mm × 15 mm) and kept for solidifying to yield a thickness of 6 mm. Trichophyton mentagrophyte (ATCC 24953) suspension was cultured on potato dextrose agar medium and incubated at 28 °C for 10 days as described previously [ 42 ]. SDA plates were inoculated by placing a sterile cotton-tipped applicator in a suspension containing spores (1.0 × 10 6 CFU/mL) and spreading it over the plate surface and being permitted to dry for 15 min.…”