Dry Powder Inhalers for Proteins Using Cryo-Milled Electrospun Polyvinyl Alcohol Nanofiber Mats

To enable the efficient delivery of drugs to the lungs, the drug particle design for most dry powder inhalers (DPIs) involves reducing the aerodynamic particle size to a few microns using methods such as spray-drying or jet-milling. Stresses, including heat and the shear forces generated by the prep...

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Bibliographic Details
Published inMolecules (Basel, Switzerland) Vol. 27; no. 16; p. 5158
Main Authors Ito, Takaaki, Yamazoe, Eriko, Tahara, Kohei
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 12.08.2022
MDPI
Subjects
Aerosols
Chymotrypsin
Denaturation
Drug delivery
Drug development
Drugs
Drying
Electrospinning
Enzymatic activity
Enzymes
Freezing
Inhalation
Inhalers
milling
Nanofibers
Particle size
Peptides
Pharmaceuticals
Polymers
Polyvinyl alcohol
Powders
protein delivery
protein formulation
Proteins
pulmonary drug delivery
Respiration
Shear forces
stability
Japan
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Summary:To enable the efficient delivery of drugs to the lungs, the drug particle design for most dry powder inhalers (DPIs) involves reducing the aerodynamic particle size to a few microns using methods such as spray-drying or jet-milling. Stresses, including heat and the shear forces generated by the preparation processes, may result in the degradation and denaturation of drugs such as those based on peptides and proteins. Here, we showed that cryo-milled polyvinyl alcohol nanofiber mats loaded with α-chymotrypsin by electrospinning exhibited suitable inhalation properties for use in DPIs, while maintaining enzymatic activity. The cryo-milled nanofiber mats were porous to fine particles, and the particle size and drug stability depended on the freezing and milling times. The median diameter of the milled fiber mats was 12.6 μm, whereas the mass median aerodynamic diameter was 5.9 μm. The milled nanofiber mats were successfully prepared, while retaining the enzymatic activity of α-chymotrypsin; 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. This novel method may be suitable for the DPI preparation of various drugs because it avoids the heating step during the DPI preparation process.
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ISSN:1420-3049
1420-3049
DOI:10.3390/molecules27165158