Formulation and In Vivo Evaluation of Effervescent Inhalable Carrier Particles for Pulmonary Delivery of Nanoparticles

Abstract

The purpose of this study was to evaluate the safety of a new inhalable effervescent carrier preparation containing model nanoparticles. Spray-freeze drying was used to prepare inhalable powders containing butylcyanoacrylate nanoparticles. The particle size of the nanoparticles before incorporation into the effervescent carrier and after dissolving the carrier powder was measured using laser light scattering. The particle size distribution of the effervescent carrier aerosol particles was measured using a cascade impactor. The prepared powder was tested in vivo using five Balb/c nude mice. The animals were treated with 1 mg of inhalable powder every week for 4 weeks. The body weight and morbidity score of the mice were observed over an 8-week period. The effervescent activity of the inhalable nanoparticle powder was observed when the powder was exposed to humidity. The particle size of the nanoparticles did not change significantly after spray-freeze drying. The mass median aerodynamic diameter (MMAD) of the prepared powder was 4.80 ± 2.12 μm, which is suitable for lung delivery. The animals that were treated with effervescent powder tolerated the administration without any changes in their morbidity scores. Our pilot study demonstrates that pulmonary nanoparticle delivery via effervescent carrier particles appears safe in the present animal model.

Keywords:

• nanoparticle
• pulmonary delivery
• carrier particles
• effervescent
• cyanoacrylate

ACKNOWLEDGMENT

This study was supported by a NSERC strategic grant, Alberta Cancer Board, and the University of Alberta. Shirzad Azarmi was supported by the Strategic Training Program in Translational Cancer Research, a partnership between CIHR, the Alberta Cancer Board, and the National Cancer Institute of Canada. The authors thank Helena Orszanska for her help in spray-freeze drying and measuring aerodynamic particle sizes.