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

Abstract

Objective

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.

Methods

Itz-NLCs were prepared by the emulsification-evaporation method using oleic acid and glycerol monostearate as liquid and solid lipids, respectively.

Results

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 < .001). A rabbit pharmacokinetic investigation revealed that Itz-NLCs have an 83.05% absolute bioavailability after intratracheal instillation.

Conclusions

The purpose of Itz-NLCs is to enhance the bioavailability and permeability of Itz in vitro for administration via the lungs.

Graphical Abstract

Keywords:

• Itraconazole
• nanostructured lipid carriers
• permeability
• pulmonary drug delivery
• bioavailability

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was financially supported by the Natural Science Foundation of Heilongjiang Province of China (Grant No. H2018013) and Outstanding Young Talents Funding of College of Pharmacy, Harbin Medical University (Grant No. 2019-JQ-03) and Shanghai Qingpu District Talent Training Medical Garden Rising Star Project (WY2019-17).