Preparation and in Vitro Evaluation of Inhalation Powder Containing Fluconazole Nanoparticles for the Treatment of Fungal Lung Infections
Immunocompromised persons are very susceptible to fungal infections. It is desirable to treat pulmonary fungal infections with specific delivery of drugs to the lungs.
Zein nanoparticles containing fluconazole were prepared by anti-solvent method. Their physico-chemical properties were investigated. From the optimal formulation, dry powder was prepared with lactose or mannitol using spray drying and aerosolization characteristics of the dry powders were evaluated using Anderson's cascade impactor. Antifungal effect was investigated against candida albicans and minimum inhibitory concentration was determined. Cytotoxicity of free fluconazole, dry powder containing drug loaded nanoparticles, dry powder containing nanoparticles without drug was also evaluated against A549 cell line by MTT method.
The size of nanoparticles was in the range of 88.70 ± 1.35 to 226.90 ± 5.40 nm, and the percentage of loading efficiency was in the range of 57.58 ± 3.61 to 92.94 ± 0.34. In the prepared dry powder samples, all the powder samples had a high emitted dose percentage. Cytotoxicity test showed that in general none of the groups had significant cytotoxic effects even at the highest studied concentration.
Using lactose as carrier, can improve the aerodynamic properties of dry powder compared with mannitol. The prepared inhaled fluconazole powder has a suitable fine particle fraction % and a low median mass aerodynamic diameter and can be well deposited in the lung. In addition, powder containing fluconazole was safe and its effect was comparable with fluconazole.
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