Next-generation drug delivery systems for aspergillosis: Overcoming barriers in antifungal therapy

Aspergillosis is a group of diseases caused primarily by Aspergillus fumigatus, an opportunistic fungal pathogen recently classified as a critical priority by the World Health Organization (WHO) due to its global impact on morbidity and mortality. The respiratory tract, particularly the nose, sinuses, and lungs, is the primary site of colonization and infection, where aspergillosis manifests in a spectrum of clinical forms, from allergic reactions to invasive disease. Steroidal drugs are commonly used to treat allergic forms, while azole antifungals remain the first-line therapy for invasive aspergillosis. However, current treatments face significant limitations, including poor bioavailability, systemic toxicity, and rising azole resistance. This review highlights recent advancements in drug delivery technologies aimed at overcoming the limitations of conventional therapies and improving outcomes in both allergic and invasive forms of aspergillosis. Innovative particulate delivery systems have been developed to enhance drug targeting, prolong release, reduce systemic exposure, and minimize side effects. These platforms include powder microparticles, polymeric nanoparticles, micelles, and various lipid-based carriers such as liposomes, solid lipid nanoparticles, and nanostructured lipid carriers for the pulmonary delivery of antifungals for invasive disease via nebulizers or dry powder inhalers (DPIs). Key antifungals incorporated into these systems include itraconazole, voriconazole, and amphotericin B. Although aerosolized antifungal therapy is not yet standard clinical practice, growing preclinical evidence supports its potential. Continued research into inhalation-based treatments could significantly reshape the therapeutic landscape for aspergillosis.