TY - JOUR
T1 - Design and development of innovative microparticulate/nanoparticulate inhalable dry powders of a novel synthetic trifluorinated chalcone derivative and Nrf2 agonist
AU - Muralidharan, Priya
AU - Jones, Brielle
AU - Allaway, Graham
AU - Biswal, Shyam S.
AU - Mansour, Heidi M.
N1 - Funding Information:
The authors gratefully acknowledge financial support from the College of Pharmacy graduate student fellowship awarded to PM. This work was partially supported by a Maryland TEDCO (Technology Development Corporation) grant award to Curveda LLC, NIH NHLBI R41HL122004 (Cureveda LLC), NIH NIAMS R41AR066418 (Cureveda LLC), NIH NIDDK R43DK098984 (Cureveda LLC), NIH NIAID HHSN2272201000033I/ HHSN27200002 A65 (HMM), NIH NIA R21AG054766 (HMM), and NIH NHLBI R01HL137282 (HMM).
Funding Information:
SEM images and data were collected in the W.M. Keck Center for Nano-Scale Imaging in the Department of Chemistry and Biochemistry at the University of Arizona with funding from the W.M. Keck Foundation Grant. All Raman data was collected in the Imaging Cores—Materials Imaging and Characterization Facility supported by the office of Research, Discovery and Innovation at the University of Arizona. This material is based upon work supported by the National Science Foundation under Grant Number #0619599 and Arizona Proposition 301: Technology and Research Initiative Fund (A.R.S.§15-1648). X-ray diffraction data were collected in the X-Ray Diffraction Facility of the Department of Chemistry and Biochemistry, The University of Arizona. The authors sincerely thank Dr. Brooke Beam-Masani, Dr. Paul Wallace and Dr. Andrei Astachkine for core facility access and assistance.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12
Y1 - 2020/12
N2 - Chalcone 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 °C. Furthermore, the results demonstrate that these innovative TMC dry powder particles are suitable for targeted delivery to the airways by inhalation.
AB - Chalcone 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 °C. Furthermore, the results demonstrate that these innovative TMC dry powder particles are suitable for targeted delivery to the airways by inhalation.
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U2 - 10.1038/s41598-020-76585-2
DO - 10.1038/s41598-020-76585-2
M3 - Article
C2 - 33188247
AN - SCOPUS:85095946243
SN - 2045-2322
VL - 10
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 19771
ER -