title: Microparticulate/Nanoparticulate Powders of a Novel Nrf2 Activator and an Aerosol Performance Enhancer for Pulmonary Delivery Targeting the Lung Nrf2/Keap-1 Pathway.
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) forin vitropredictive 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. Usingin vitropredictive 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.
authors: College of Pharmacy, Skaggs Pharmaceutical Sciences Center, The University of Arizona, Tucson, AZ, 85721, USA.
authors: Priya
authors: P
authors: Muralidharan
authors: Departments of Pediatrics and Internal Medicine, Lung and Heart-Lung Transplant Programs, The Ohio State University College of Medicine, Columbus, OH 43205, USA; The Davis Heart and Lung Research Institute, The Ohio State University College of Medicine, Columbus, OH 43205, USA.
authors: Don
authors: D
authors: Hayes
authors: Department of Medicine, Division of Translational and Regenerative Medicine, The University of Arizona, Tucson, AZ, 85724, USA.
authors: Stephen M
authors: SM
authors: Black
authors: College of Pharmacy, Skaggs Pharmaceutical Sciences Center, The University of Arizona, Tucson, AZ, 85721, USA; Institute of the Environment, The University of Arizona, Tucson, AZ 85721, USA; National Cancer Institute Comprehensive Cancer Center, The University of Arizona, Tucson, AZ 85721, USA; The BIO5 Research Institute, The University of Arizona, Tucson, AZ 85721, USA.
authors: Heidi M
authors: HM
authors: Mansour
keywords: acute lung injury (ALI); chronic obstructive pulmonary disease (COPD); dry powder inhaler (DPI); human inhaler device; in vitro aerosol predictive lung deposition modeling; nanotechnology; pulmonary endothelial disease; pulmonary hypertension (PH); solid state particle engineering design; targeted pulmonary drug delivery