Itraconazole-loaded nanostructured lipid carriers (NLC) for pulmonary treatment of aspergillosis in falcons.

Abstract

Aspergillosis is the most common and most lethal disease in captive falcons, which is most effectively treated with the poorly soluble drug Itraconazole. To obtain a high drug concentration at the side of infection, the falcon's respiratory system, an isotonic, sterile, non-toxic NLC formulation loaded with Itraconazole was developed for pulmonary application. Itraconazole-loaded NLC had a particle size well in the nanometer range and possessed a narrow particle size distribution. An entrapment efficiency of 99.98% was achieved. A good storage stability of the formulation over 6months was found. Neither by MTS nor by LDH assay cytotoxic effects were determined on the cell line A549, indicating a good tolerability after inhalation. No physical instabilities of Itraconazole-loaded NLC could be detected nebulizing the formulation with a new nanonebulizer into a therapeutic chamber for the treatment of falcons. It could be shown, that the particle size of the aerosol generated nebulizing Itraconazole-loaded NLC with the nanonebulizer was in the nanometer range, providing the possibility to penetrate into the respiratory tract of falcons. By scintigraphy deposition of Itraconazole-loaded NLC in the lung and the air sacs of a patient was shown, being a prerequisite for the pulmonary treatment of aspergillosis in falcons.