Polishing the Therapy of Onychomycosis Induced by Candida spp.: Amphotericin B-Loaded Nail Lacquer

Abstract

Onychomycosis induced by Candida spp. has several limitations regarding its treatment. Nail lacquers display the potential to overcome these drawbacks by providing therapeutic compliance and increasing local drug bioavailability. Thus, this work aimed to produce a nail lacquer loaded with Amphotericin B (AmB) and evaluate its performance. The AmB-loaded nail lacquer was produced and preliminarily characterized. An AmB quantification method was developed. Stability, drug release, permeability and anti-Candida activity assays were conducted. The analytical method validation met the acceptance criteria. The drug loading efficiency was 100% (0.02 mg/g of total product), whereas the AmB stability was limited to ≅7 days (≅90% remaining). The nail lacquer displayed a drying time of 187 s, non-volatile content of around 20%_w/w, water-resistance of approximately 2%_w/w of weight loss and satisfactory in vitro adhesion. Moreover, the in vitro antifungal activity against different Candida spp. strains was confirmed. The AmB release and the ex vivo permeability studies revealed that AmB leaves the lacquer and permeates the nail matrix in 47.76 ± 0.07% over 24 h. In conclusion, AmB-loaded nail lacquer shows itself as a promising extemporaneous dosage form with remarkable anti-Candida activity related to onychomycosis.

Keywords: Candida spp.; amphotericin B; extemporaneous product; nail infection; nail lacquer; onychomycosis.

Scheme 1

Overall ungueal anatomy and its correlation to the mechanism of action of nail lacquers for the treatment of onychomycosis.

Scheme 2

Physicochemical characterization of the AmB-loaded nail lacquer. VA, visual aspects; DT, drying-time test; N-VC, non-volatile content test; WR, water-resistance test; BT, blush test; and IVA, in vitro adhesion test.

Scheme 3

Graphical illustration of the in vitro AmB-loaded nail lacquer’s drug release. (A) The nail lacquer was applied and left to dry for 8 h. For the release assay, 2 mL of the medium was collected at each time interval for AmB quantification (B) and immediately replaced by fresh medium (C).

Figure 1

Spectroscopic signal emitted by the AmB’s chromophore group over 90 days. (A) Wavescan profile of AmB-loaded nail lacquer. (B) AmB-loaded nail lacquer’s concentration over time.

Figure 2

Qualitative evaluation of the in vitro antifungal activity by the agar well-diffusion method. (A) Samples application scheme, (B) Candida albicans ATCC 90028, (C) C. glabrata ATCC 2001, (D) C. tropicalis ATCC 13803, (E) C. dubliniensis CBS 7987 and (F) C. parapsilosis ATCC 22019. ADN, Amphotericin B–loaded nail lacquer; AD, Amphotericin B–DMSO; F, Fungizone^®; DN, DMSO nail lacquer; D, DMSO; N, nail lacquer; S, saline solution.

Figure 3

AmB in vitro release and ex vivo permeation profiles from AmB-loaded nail lacquer. (A) AmB’s cumulative release percentage in phosphate saline buffer medium. (B) AmB’s cumulative permeation percentage across an ex vivo nail model from bovine hooves.