title: NanoCluster budesonide formulations enable efficient drug delivery driven by mechanical ventilation.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, USA.
authors.forename: Warangkana
authors.initials: W
authors.lastname: Pornputtapitak
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, USA; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-suef University, Egypt.
authors.forename: Nashwa
authors.initials: N
authors.lastname: El-Gendy
authors.affiliation: Department of Medicine Division of Pulmonary Diseases and Critical Care Medicine, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Mermis
authors.affiliation: Department of Medicine Division of Pulmonary Diseases and Critical Care Medicine, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: O'Brien-Ladner
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, USA; Department of Chemical and Petroleum Engineering, University of Kansas, Lawrence, KS, USA. Electronic address: berkland@ku.edu.
authors.forename: Cory
authors.initials: C
authors.lastname: Berkland
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D019819:Budesonide / Q000008:administration & dosage*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems; D007442:Intubation, Intratracheal; D053758:Nanoparticles; D009330:Nebulizers and Vaporizers; D011208:Powders; D012121:Respiration, Artificial / Q000379:methods*
chemical_list: D000336:Aerosols; D001993:Bronchodilator Agents; D011208:Powders; D019819:Budesonide
keywords: Budesonide; Dry powder inhalers; Inhalation; Mechanical ventilation; NanoCluster