Antifungal nanosuspensions with surfactants and silver for the treatment of onychomycosis

Eur J Pharm Biopharm. 2022 Oct:179:194-205. doi: 10.1016/j.ejpb.2022.09.004. Epub 2022 Sep 10.

Abstract

Fungal nail infection (Onychomycosis) often requires prolonged treatment and is associated with a high risk of resistance to treatment. Here in this contribution, we introduce a novel approach to enhance penetration and antifungal activity of the antifungal drug griseofulvin (GF). Solid dispersions were prepared with hydroxypropyl methylcellulose acetate succinate (HPMCAS) and combined with surfactant (either sodium dodecyl sulphate (SDS), dodecyl trimethylammonium bromide (DTAB), or Pluronic F127) using mechanochemical activation. The prepared powders were then suspended with spray-dried silica-coated silver nanoparticles and applied onto infected bovine hooves to assess permeability and antifungal activity. The results showed that the prepared nanosuspensions significantly suppressed fungal activity causing disruption of fungal biofilms. Raman mapping showed enhanced permeation while dynamic vapor sorption (DVS), and particle size measurements showed varied effects depending on the type of surfactant and milling conditions. The prepared nanosuspensions displayed enhanced solubility of the poorly soluble drug reaching approximately 1.2 mg/mL. The results showed that the dispersions that contained DTAB displayed maximum efficacy while the inclusion of colloidal silver did not seem to significantly improve the antifungal activity compared to other formulations.

Keywords: Fungal biofilms; Nail infections; Nanosuspensions; Saturation solubility; Silver nanoparticles; Solid dispersions.

MeSH terms

  • Animals
  • Antifungal Agents / pharmacology
  • Bromides
  • Cattle
  • Drug Compounding / methods
  • Excipients
  • Griseofulvin
  • Metal Nanoparticles*
  • Onychomycosis* / drug therapy
  • Particle Size
  • Poloxamer
  • Quaternary Ammonium Compounds
  • Silicon Dioxide
  • Silver
  • Sodium Dodecyl Sulfate
  • Solubility
  • Surface-Active Agents

Substances

  • Antifungal Agents
  • Bromides
  • Excipients
  • Quaternary Ammonium Compounds
  • Surface-Active Agents
  • Poloxamer
  • decyltrimethylammonium
  • Griseofulvin
  • Sodium Dodecyl Sulfate
  • Silver
  • Silicon Dioxide