Microparticulate/nanoparticulate powders of a novel Nrf2 activator and an aerosol performance enhancer for pulmonary delivery targeting the lung Nrf2/Keap-1 pathway (original) (raw)
* Corresponding authors
a College of Pharmacy, Skaggs Pharmaceutical Sciences Center, The University of Arizona, 1703 E. Mabel St, Tucson, AZ 85721-0202, USA
E-mail: mansour@pharmacy.arizona.edu
Tel: +1 520 626 2768
b Departments of Pediatrics and Internal Medicine, Lung and Heart–Lung Transplant Programs, The Ohio State University College of Medicine, Columbus, OH 43205, USA
c The Davis Heart and Lung Research Institute, The Ohio State University College of Medicine, Columbus, OH 43205, USA
d Department of Medicine, Division of Translational and Regenerative Medicine, The University of Arizona, Tucson, AZ, USA
e Institute of the Environment, The University of Arizona, Tucson, AZ 85721, USA
f National Cancer Institute Comprehensive Cancer Center, The University of Arizona, Tucson, AZ 85721, USA
g The BIO5 Research Institute, The University of Arizona, Tucson, AZ 85721, USA
Abstract
This systematic and comprehensive study reports for the first time on the successful rational design of advanced inhalable therapeutic dry powders containing dimethyl fumarate, a first-in-class Nrf2 activator drug to treat pulmonary inflammation, using particle engineering design technology for targeted delivery to the lungs as advanced spray dried (SD) one-component DPIs. In addition, two-component co-spray dried (co-SD) DMF : D-Man DPIs with high drug loading were successfully designed for targeted lung delivery as advanced DPIs using organic solution advanced spray drying in closed mode. Regional targeted deposition using design of experiments (DoE) for in vitro predictive lung modeling based on aerodynamic properties was tailored based on composition and spray drying parameters. These findings indicate the significant potential of using D-Man in spray drying to improve particle formation and aerosol performance of small molecule with a relatively low melting point. These respirable microparticles/nanoparticles in the solid-state exhibited excellent aerosol dispersion performance with an FDA-approved human DPI device. Using in vitro predictive lung deposition modeling, the aerosol deposition patterns of these particles show the capability to reach lower airways to treat inflammation in this region in pulmonary diseases such as acute lung injury (ALI), chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH), and pulmonary endothelial disease.
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Article information
DOI
https://doi.org/10.1039/C5ME00004A
Article type
Paper
Submitted
05 Nov 2015
Accepted
04 Jan 2016
First published
27 Jan 2016
This article is Open Access
Download Citation
Mol. Syst. Des. Eng., 2016,1, 48-65
Author version available
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Microparticulate/nanoparticulate powders of a novel Nrf2 activator and an aerosol performance enhancer for pulmonary delivery targeting the lung Nrf2/Keap-1 pathway
P. Muralidharan, D. Hayes, S. M. Black and H. M. Mansour,Mol. Syst. Des. Eng., 2016, 1, 48DOI: 10.1039/C5ME00004A
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