Invasive pulmonary fungal diseases: Towards formulation-optimized targeted therapeutic strategies

Invasive pulmonary fungal diseases (IPFD) represent a growing global health crisis, with escalating incidence and mortality rates, posing a particularly life-threatening risk to immunocompromised populations. The complexity of diagnosis, limited therapeutic options, and the growing challenge of antifungal resistance have significantly constrained the clinical efficacy, leading to poor patient outcomes. Recently, the integration of revolutionary drug delivery platforms with classical antifungal agents, such as optimized nebulized amphotericin B, voriconazole-loaded liposomes and inhalable amphotericin B microspheres, has demonstrated significant clinical potential, particularly in pulmonary applications, by markedly enhancing biodistribution at the infection site while substantially minimizing systemic adverse effects. This comprehensive review synthesized recent advances in IPFD research, encompassing epidemiological characteristics, molecular pathogenesis, clinical manifestations, cutting-edge diagnostic technologies (including advanced imaging, fungal-specific biomarkers and molecular techniques like polymerase chain reaction (PCR) and next-generation sequencing) as well as formulation-based therapeutics that optimize pulmonary targeting to improve efficacy and reduce systemic toxicity. This review aimed to provide insights for the future development of precision-targeted delivery mechanisms and next-generation antifungal agents.