Advancing antifungal therapy: exploring targeted CFW-PEc-enhanced ethosomal formulations of amphotericin B against cryptococcal pneumonia

Cryptococcal pneumonia presents a significant global health burden with limited therapeutic options due to inherent toxicity and suboptimal bioavailability of conventional antifungal agents. This investigation demonstrates the innovative application of calcofluor white-phosphatidylethanolamine conjugate (CFW-PEc) to enhance amphotericin B (AmB) delivery via ethosomes for cryptococcal infection treatment. Our findings elucidate that CFW-PEc significantly potentiates the antifungal efficacy of AmB-loaded ethosomes against <i>Cryptococcus neoformans</i> while concomitantly mitigating associated cytotoxicity at optimal concentrations. In murine models of pulmonary cryptococcosis, this novel formulation achieved a remarkable 10-fold reduction in fungal burden compared to controls, while preserving pulmonary histoarchitecture and attenuating inflammatory responses. This delivery system's integrated strategy of increasing antifungal effectiveness while reducing adverse effects marks a significant leap forward in developing safer and more targeted nanomaterial-mediated antifungal treatments. These results have profound implications for developing more efficacious and less toxic treatment modalities for cryptococcal pneumonia and potentially other invasive fungal infections.