Development of inhaled dry powder fluconazole and investigation of the effectiveness in the eradication of Candida albicans biofilms

Background: Candida albicans is an opportunistic pathogen that causes a wide range of fungal infections including invasive pulmonary candidiasis, particularly in immunocompromised patients. Treatment of such infections is challenging because of the ability of C. albicans to form biofilms, which are more tolerant to treatment with antifungal drugs. Pulmonary candidiasis is currently treated systemically, but inhaled antifungals could have the major advantage of delivery of a high concentration directly at the site of infection. The major purpose of this study was to develop a novel dry powder formulation of fluconazole suitable for inhalation and to test the effectiveness of this formulation on C. albicans  biofilms.

Methods Two approaches were used, pharmaceutical approach, electrospraying, an electrohydrodynamic technique, was used to produce micro-sized fluconazole particles. Microbiological approach, colony biofilm assay was used to grow Candida albicans biofilm.

Results: The results showed that the electrosprayed fluconazole particles had a median geometric diameter of 6.9 µm (size range of 4.0 - 13.4 µm). Powder X-ray diffraction suggested the presence of amorphous material or nanocrystals. The activity of these particles on C. albicans biofilm demonstrated similar or better efficacy when compared to the activity of unprocessed crystalline fluconazole (median particle diameter 112 µm; size range 41- 339 µm) against biofilms.

Conclusions: The results supported the potential use of electrosprayed fluconazole dry powder formulations in the treatment of pulmonary candidiasis or other fungal lung infections.