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Pulmonary aspergillosis, which is a secondary complication of fungal pneumonia, is widely considered to have an increasing incidence and high mortality. Itraconazole (Itz) can inhibit ergosterol biosynthesis to treat pulmonary aspergillosis. Nevereless, Itz’s clinical application is limited because of its poor water solubility, low oral bioavailability, and systemic hepatotoxicity. In this study, Itz-loaded nanostructured lipid carriers (Itz-NLCs) were developed to improve the  in vitro  permeability and bioavailability of Itz  via  pulmonary administration. Itz-NLCs were prepared by the emulsification-evaporation method using oleic acid and glycerol monostearate as liquid and solid lipids, respectively. The Itz-NLCs were optimized with tiny particle size, uniform distribution, and excellent entrapment efficiency ( EE , 97.57% ± 0.45%). A Xenopus alveolar membrane was used in the permeation study, and the cumulative permeation percentage of Itz was 10% for Itz-NLCs at 8 h, which was 2.50-fold higher than that for Itz suspensions (4%,  p  &lt; .001). A rabbit pharmacokinetic investigation revealed that Itz-NLCs have an 83.05% absolute bioavailability after intratracheal instillation. The purpose of Itz-NLCs is to enhance the bioavailability and permeability of Itz  in vitro  for administration  via  the lungs.

In vivo and in vitro evaluation of pulmonary administration of itraconazole nanostructured lipid carriers for pulmonary aspergillosis