Design and development of innovative microparticulate/nanoparticulate inhalable dry powders of a novel synthetic trifluorinated chalcone derivative and Nrf2 agonist.
AffiliationUniv Arizona, Coll Pharm
Univ Arizona, Coll Med
Univ Arizona, Coll Med, Dept Med, Div Translat & Regenerat Med
Univ Arizona, BIO5 Res Inst
Univ Arizona, Inst Environm
Univ Arizona, Natl Canc Inst Comprehens Canc Ctr
MetadataShow full item record
CitationMuralidharan, P., Jones, B., Allaway, G., Biswal, S. S., & Mansour, H. M. (2020). Design and development of innovative microparticulate/nanoparticulate inhalable dry powders of a novel synthetic trifluorinated chalcone derivative and Nrf2 agonist. Scientific Reports, 10(1), 1-15.
Rights© The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractChalcone derivatives are shown to possess excellent anti-inflammatory and anti-oxidant properties which are of great interest in treating respiratory diseases such as acute lung injury (ALI), acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis (PF). This study successfully designed and developed dry powder inhaler (DPI) formulations of TMC (2-trifluoromethyl-2 ' -methoxychalone), a new synthetic trifluorinated chalcone and Nrf2 agonist, for targeted pulmonary inhalation aerosol drug delivery. An advanced co-spray drying particle engineering technique was used to design and produce microparticulate/nanoparticulate formulations of TMC with a suitable excipient (mannitol) as inhalable particles with tailored particle properties for inhalation. Raw TMC and co-spray dried TMC formulations were comprehensively characterized for the first time using scanning electron microscopy (SEM) with energy dispersive X-ray (EDX) spectroscopy, thermal analysis, X-ray powder diffraction (XRPD), and molecular fingerprinting as dry powders by ATR-FTIR spectroscopy and Raman spectroscopy. Further, biocompatibility and suitability of formulations were tested with in vitro cellular transepithelial electrical resistance (TEER) in air-interface culture (AIC) using a human pulmonary airway cell line. The ability of these TMC formulations to perform as aerosolized dry powders was systematically evaluated by design of experiments (DOEs) using three different FDA-approved human inhaler devices followed by interaction parameter analyses. Multiple spray drying pump rates (25%, 75%, and 100%) successfully produced co-spray dried TMC:mannitol powders. Raw TMC exhibited a first-order phase transition temperature at 58.15 +/- 0.38 degrees C. Furthermore, the results demonstrate that these innovative TMC dry powder particles are suitable for targeted delivery to the airways by inhalation.
NoteOpen access journal
VersionFinal published version
Except where otherwise noted, this item's license is described as © The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License.
- Design, physicochemical characterization, and optimization of organic solution advanced spray-dried inhalable dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine poly(ethylene glycol) (DPPE-PEG) microparticles and nanoparticles for targeted respiratory nanomedicine delivery as dry powder inhalation aerosols.
- Authors: Meenach SA, Vogt FG, Anderson KW, Hilt JZ, McGarry RC, Mansour HM
- Issue date: 2013
- Design, characterization, and aerosol dispersion performance modeling of advanced spray-dried microparticulate/nanoparticulate mannitol powders for targeted pulmonary delivery as dry powder inhalers.
- Authors: Li X, Vogt FG, Hayes D Jr, Mansour HM
- Issue date: 2014 Apr
- Physicochemical characterization and aerosol dispersion performance of organic solution advanced spray-dried microparticulate/nanoparticulate antibiotic dry powders of tobramycin and azithromycin for pulmonary inhalation aerosol delivery.
- Authors: Li X, Vogt FG, Hayes D Jr, Mansour HM
- Issue date: 2014 Feb 14
- Advanced therapeutic inhalation aerosols of a Nrf2 activator and RhoA/Rho kinase (ROCK) inhibitor for targeted pulmonary drug delivery in pulmonary hypertension: design, characterization, aerosolization, <i>in vitro</i> 2D/3D human lung cell cultures, and <i>in vivo</i> efficacy.
- Authors: Acosta MF, Muralidharan P, Grijalva CL, Abrahamson MD, Hayes D Jr, Fineman JR, Black SM, Mansour HM
- Issue date: 2021 Jan-Dec
- Advanced spray-dried design, physicochemical characterization, and aerosol dispersion performance of vancomycin and clarithromycin multifunctional controlled release particles for targeted respiratory delivery as dry powder inhalation aerosols.
- Authors: Park CW, Li X, Vogt FG, Hayes D Jr, Zwischenberger JB, Park ES, Mansour HM
- Issue date: 2013 Oct 15