Development of Porous Inhalation Powder Using Electrospun Nanofiber Mats

Abstract

Dry powder inhalers (DPIs) require controlled aerodynamic diameters of 1 to 6 μm in order for the powder particles to deliver to the deep lungs. However, single-micron particles are difficult to release from inhalers due to their high degree of adhesion and aggregation. In addition, conventional DPI preparation methods cannot be applied to heat-sensitive drugs because they require processing at high temperatures. In this study, we focused on the electrospun technique. The applicant showed that cryo-milled polyvinyl alcohol nanofiber mats loaded with α-chymotrypsin (α-Chy) by electrospinning exhibited suitable inhalation properties for use in DPIs, while maintaining enzymatic activity. Porous particles with geometric diameters ranging from 10 to 35 μm were prepared to reduce adhesion. The in vitro aerosol performance of the milled nanofiber mats using a cascade impactor showed that the aerodynamic particle size was smaller (5.9 μm) than the geometric diameter, making the aerodynamic diameter suitable for DPI. The milled nanofiber mats maintained the enzymatic activity of α-Chy. Furthermore, the activity of milled fiber mats that had been stored for 6 months was comparable to the activity of those that were freshly prepared.

Graphical Abstract

Scanning electron micrographs of the electrospun nanofiber mats and milled nanofiber mats. (a) A polyvinyl alcohol (PVA) nanofiber mat prepared using the electrospinning technique. (b) A PVA nanofiber mat milled by cryo-milling (freezing: 30 min, milling: 3 min).