Inhalable Nanoparticles/Microparticles of an AMPK and Nrf2 Activator for Targeted Pulmonary Drug Delivery as Dry Powder Inhalers.

The AAPS Journal
Maria F AcostaHeidi M Mansour

Abstract

Metformin is an activator of the AMPK and Nrf2 pathways which are important in the pathology of several complex pulmonary diseases with unmet medical needs. Organic solution advanced spray drying in the absence of water in closed-mode was used to design and develop respirable dry powders. Following comprehensive characterization, the influence of physicochemical properties was correlated with performance as aerosols using inertial impaction and three different human dry powder inhaler (DPI) devices varying in device properties. In vitro cell assays were conducted to test safety in 2D human pulmonary cell lines and in 3D small airway epithelia comprising primary cells at the air-liquid interface (ALI). In addition, in vitro transepithelial electrical resistance (TEER) was carried out. Metformin remained crystalline following advanced spray drying under these conditions. All SD powders consisted of nanoparticles/microparticles in the solid state. In vitro aerosol dispersion performance showed high aerosolization for all SD metformin powders with all DPI devices tested. High emitted dose for all powders with all three DPI devices was measured. Differences in other aerosol performance parameters and the interplay between the proper...Continue Reading

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Methods Mentioned

BETA
scanning electron microscopy
X-ray
Infrared Spectroscopy
Assay
Light Diffraction

Software Mentioned

Expert®
SYSTAT
Design
[UNK] Pro
SigmaPlot

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