Itraconazole Loaded Biosurfactin Micelles with Enhanced Antifungal Activity: Fabrication, Evaluation and Molecular Simulation

Abstract

Itraconazole (ITZ) is a broad-spectrum antifungal for superficial subcutaneous and systemic fungal infections. This study aimed to enhance the antifungal activity of ITZ using surfactin A (SA), a cyclic lipopeptide produced by the SA-producing Bacillus strain NH-100, possessing strong antifungal activity. SA was extracted, and ITZ-loaded SA micelles formulations were prepared via a single-pot rinsing method and characterized by particle size, zeta potential, and infrared spectroscopy. In vitro dissolution at pH 1.2, as well as hemolysis studies, was also carried out. The fabricated formulations were stable and non-spherical in shape, with an average size of about 179 nm, and FTIR spectra depicted no chemical interaction among formulation components. ITZ-loaded micelles showed decreased hemolysis activity in comparison to pure ITZ. The drug released followed the Korsmeyer–Peppas model, having R2 0.98 with the diffusion release mechanism. In an acidic buffer, drug release of all prepared formulations was in the range of 73–89% in 2 h. The molecular simulation showed the outstanding binding and stability profile of the ITZ-SA complex. The aromatic ring of the ITZ mediates a π-alkyl contact with a side chain in the SA. It can be concluded that ITZ-loaded micelles, owing to significant enhanced antifungal activity up to 6-fold due to the synergistic effect of SA, can be a promising drug delivery platform for delivery of poorly soluble ITZ.

Application of Biosurfactants in Medical Sciences

“…Although ITZ can pose potential side effects due to its pronounced hemolytic activity, the low hemolytic activity of surfactin A could effectively mitigate this risk. When encapsulating ITZ within surfactin A micelles, the direct contact between the drug and red blood cells is restricted, which results in a 53 ± 2.63% reduction in hemolytic activity compared to a similar solution-based concentration and significantly improves the antimicrobial efficacy against Aspergillus fumigatus , Aspergillus niger , and Candida albicans [ 15 ]. Therefore, for hydrophobic drugs, using biosurfactants as their carrier components not only improves the drug’s bioavailability and reduces its side effects, but also has a synergistic effect on increasing drug efficacy.…”