4 research outputs found
Antifungal nanosuspensions with surfactants and silver for the treatment of onychomycosis.
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. [Abstract copyright: Copyright © 2022. Published by Elsevier B.V.
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Antifungal nanosuspensions with surfactants and silver for the treatment of onychomycosis
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 dis- played 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
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Generation of High Dose Inhalable Effervescent Dispersions against Pseudomonas aeruginosa Biofilms
Purpose: Novel particle engineering approach was used in this study to generate high dose inhalable effervescent particles with synergistic effects against Pseudomonas aeruginosa biofilms. Methods: Spray dried co-amorphous salt of ciprofloxacin (CFX) and tartaric acid (TA) was prepared and coated with external layer of sodium bicarbonate and silica coated silver nanobeads. Design of experiments (DOE) was used to optimize physicochemical properties of particles for enhanced lung deposition. Results: Generated particles were co-amorphous CFX/TA showing that CFX lost its zwitterionic form and exhibiting distinct properties to CFX/HCl as assessed by FTIR and thermal analysis. Particles exhibited mass mean aerodynamic diameter (MMAD) of 3.3 μm, emitted dose of 78% and fine particle dose of 85%. Particles were further evaluated via antimicrobial assessment of minimum inhibitory concentrations (MIC) and minimum biofilm eradication concentration (MBEC). MIC and MBEC results showed that the hybrid particles were around 3–5 times more effective when compared to CFX signifying that synergistic effect was achieved. Diffusing wave spectroscopy results showed that the silver containing particles had a disruptive effect on rheological properties as opposed to silver free particles. Conclusions: Overall, these results showed the potential to use particle engineering to generate particles that are highly disruptive of bacterial biofilms
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Griseofulvin solvate solid dispersions with synergistic effect against fungal biofilms
Fungal biofilms are invariably recalcitrant to antifungal drugs and thus can cause recurrent serious infections. The aim of this work was to prepare highly effective form of the antifungal drug griseofulvin using the chloroform solvate embedded into different polymeric matrices. Based on their solid solubility, solvated (chloroform) and non-solvated (methanol and acetone) solid dispersions were prepared using different materials: silica, microcrystalline cellulose, polyvinylpyrrolidone and hydroxypropyl methylcellulose acetate succinate (HPMCAS) by which HPMCAS dispersions showed the highest solubility of about 200 μg/mL compared with ∼30 μg/mL for pure griseofulvin. The anti fungal potential of griseofulvin was assessed against the dermatophytes T. rubrum. Metabolic and protease activity of T. rubrum NCPF 935 with and without the presence of GF:HPMCAS chloroform solvates showed significant reduction compared to the untreated control after 24 h period. Confocal laser scanning microscopy showed thin hyphae compared to Control and GF:HPMCAS (non solvated). Dynamic vapour sorption data showed that HPMCAS formed most stable solvate structure preventing recrystallization and solvate expulsion, which could explain the disruptive effect of the biofilms. This could be explained by the formed hydrogen bonds as revealed by the solid and liquid state NMR data, which was further confirmed via thermal and FTIR analyses