PURPOSE: A nebulized aerosol formulation of the anti-cancer agent farnesol is developed and shown to induce cell death of human lung cancer cells in vitro. METHODS: A nebulized farnesol formulation containing polysorbate 80 (Tween 80) is developed. The measurements of the aerosol properties during nebulization were used as input for a mathematical model of airway surface liquid in the lung of an average adult, to estimate the airway surface liquid drug concentration of the deposited farnesol. Cytotoxicity of the formulations was measured in vitro on non-small cell lung cancer cells (H460 and A549). RESULTS: As much as 100% of lung cancer cytotoxicity can be achieved by using Pari LC Star and LC Plus nebulizers. The estimated airway surface liquid concentrations of the deposited farnesol reveal that the IC50 of the nebulized farnesol can be achieved over the entire tracheobronchial region, using the above Pari nebulizers with a volume fill of 5 ml. CONCLUSIONS: Drug concentrations higher than IC50 in the airway surface liquid are predicted with our methods, suggesting in vivo trials of a formulation may be warranted with these particular nebulizers.
PURPOSE: A nebulized aerosol formulation of the anti-cancer agent farnesol is developed and shown to induce cell death of humanlung cancer cells in vitro. METHODS: A nebulized farnesol formulation containing polysorbate 80 (Tween 80) is developed. The measurements of the aerosol properties during nebulization were used as input for a mathematical model of airway surface liquid in the lung of an average adult, to estimate the airway surface liquid drug concentration of the deposited farnesol. Cytotoxicity of the formulations was measured in vitro on non-small cell lung cancer cells (H460 and A549). RESULTS: As much as 100% of lung cancercytotoxicity can be achieved by using Pari LC Star and LC Plus nebulizers. The estimated airway surface liquid concentrations of the deposited farnesol reveal that the IC50 of the nebulized farnesol can be achieved over the entire tracheobronchial region, using the above Pari nebulizers with a volume fill of 5 ml. CONCLUSIONS: Drug concentrations higher than IC50 in the airway surface liquid are predicted with our methods, suggesting in vivo trials of a formulation may be warranted with these particular nebulizers.
Authors: Mark A Scheper; Mark E Shirtliff; Timothy F Meiller; Brian M Peters; Mary Ann Jabra-Rizk Journal: Neoplasia Date: 2008-09 Impact factor: 5.715