title: Formulation and characterization of spray-dried powders containing nanoparticles for aerosol delivery to the lung.
abstract: Spray-drying is a common practice of powder preparation for a wide range of drugs. Spray-dried powders can be used to deliver particles to the lungs via a dry powder inhaler (DPI). The present study investigated the feasibility of developing a platform for aerosol delivery of nanoparticles. Lactose was used as the excipient and spray-dried with two different types of nanoparticles: gelatin and polybutylcyanoacrylate nanoparticles. Results showed that some carrier particles were hollow while others had a continuous matrix. Gelatin nanoparticles were incorporated throughout the matrix and sometimes accumulated at one end of the lactose. Polycyanoacrylate nanoparticles mostly clustered in different spots within the lactose carriers. The mean sizes of both nanoparticle types were characterized at two different times: before they were spray-dried and after they were redissolved from the spray-dried powders. Both nanoparticle types remained in the nano-range size after spray-drying. The mean nanoparticle sizes were increased by approximately 30% after spray-drying, though this increase was statistically significant only for the gelatin nanoparticles. Dispersion of the powder with an in-house passive dry powder inhaler and subsequent cascade impaction measurements showed that incorporation of the nanoparticles did not affect the fine particle fraction (FPF) or mass median aerodynamic diameter (MMAD) of the powders. FPF was approximately 40% while MMAD was 3.0+/-0.2 microm, indicating the present formulations yield aerosols of a suitable particle size for efficient lung delivery of nanoparticles. The present work demonstrates that nanoparticles can be delivered to the lungs via carrier particles that dissolve after coming in contact with the aqueous environment of the lung epithelium. This opens the way for new drug-targeting strategies using nanoparticles for pulmonary delivery of drugs and diagnostics.
authors.affiliation: Department of Radiation Oncology, Cross Cancer Institute, Edmonton, Alta., Canada T6G 1Z2.
authors.forename: Jeffrey O-H
authors.initials: JO
authors.lastname: Sham
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Warren H
authors.initials: WH
authors.lastname: Finlay
authors.forename: Wilson H
authors.initials: WH
authors.lastname: Roa
authors.forename: Raimar
authors.initials: R
authors.lastname: Löbenberg
mesh_terms: D000336:Aerosols; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004337:Drug Carriers; D005780:Gelatin; D006801:Humans; D007785:Lactose / Q000008:administration & dosage*; D008168:Lung; D010316:Particle Size; D011208:Powders
chemical_list: D000336:Aerosols; D004337:Drug Carriers; D011208:Powders; D005780:Gelatin; D007785:Lactose