Pharmaceutical NanotechnologyNanoCluster budesonide formulations enable efficient drug delivery driven by mechanical ventilation

Agglomerates of budesonide nanoparticles (also known as 'NanoClusters') are fine dry powder aerosols that were hypothesized to enable drug delivery through ventilator circuits. These engineered powders were delivered via a Monodose® inhaler or a novel device, entrained through commercial endotracheal tubes, and analyzed by cascade impaction. Inspiration flow rates and other parameters such as inspiration patterns and inspiration volumes were controlled by a ventilator. NanoCluster budesonide (NC-Bud) formulations had a higher efficiency of aerosol delivery compared to micronized budesonide with NC-Bud showing a much higher percent emitted fraction (%EF). Different inspiration patterns (sine, square, and ramp) did not affect the powder performance of NC-Bud when applied through a 5.0 mm endotracheal tube. The aerosolization of NC-Bud also did not change with the inspiration volume (1.5-2.5 L) nor with the inspiration flow rate (20-40 L/min) suggesting fast emptying times for budesonide capsules. The %EF of NC-Bud was higher at 51% relative humidity compared to 82% RH. The novel device and the Monodose® showed the same efficiency of drug delivery but the novel device fit directly to a ventilator and endotracheal tubing connections. The new device combined with NanoCluster formulation technology allowed convenient and efficient drug delivery through endotracheal tubes.

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