Recent Developments in Inhaled Triazoles Against Invasive Pulmonary Aspergillosis

Abstract

Invasive pulmonary aspergillosis (IPA) presents high incidence and high mortality in immunocompromised patients. To combat or prevent IPA, triazoles such as voriconazole or itraconazole and posaconazole are becoming the first-or second-line therapy, respectively.However, triazoles present issues of oral bioavailability, high liver metabolism and/or drugdrug interactions, increasing the variability of systemic concentrations. To overcome these issues, inhalation is a promising route for delivering triazoles for prophylactic or curative therapy of IPA. Indeed, pulmonary drug delivery increases the drug in situ drastically while decreasing the systemic exposure, therefore limiting drug metabolisation, side effects and drug-drug interactions. Development of triazoles for inhalation has focused on voriconazole and itraconazole, drugs which are both highly permeable but present high solubility differences. In this review, the most complete and promising pharmaceutical developments for voriconazole and itraconazole are described.Keywords: aerosol, antifungal, aspergillosis, fungal infection, pulmonary delivery, dry powder inhaler, dry powder for inhalation, nebulizer, nebulization, cyclodextrin, nanoparticle, solid dispersion, controlled release drug delivery. Abbreviations: AI90H, amorphous itraconazole with Phospholipon

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