Evidence map›Paper›PMID 33188247›Full record

ArticleScientific reports2020

Design and development of innovative microparticulate/nanoparticulate inhalable dry powders of a novel synthetic trifluorinated chalcone derivative and Nrf2 agonist.

Priya Muralidharan, Brielle Jones, Graham Allaway, Shyam S Biswal, Heidi M Mansour

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.8field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 8 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 4 institutions in 1 country.

Priya MuralidharanColleges of Pharmacy and Medicine, University of Arizona, 1703 E. Mabel St, Tucson, AZ, 85721, USA.
Brielle JonesCureveda LLC, Halethorpe, MD, USA.
Graham AllawayCureveda LLC, Halethorpe, MD, USA.
Shyam S BiswalDepartment of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Heidi M MansourColleges of Pharmacy and Medicine, University of Arizona, 1703 E. Mabel St, Tucson, AZ, 85721, USA. mansour@pharmacy.arizona.edu.
Cureveda (United States) · USAmerican Association of Colleges of Pharmacy · USJohns Hopkins Medicine · USNational Cancer Institute · US

Funding

Perinatal NO signaling in congenital heart diseaseR01HL137282 · NHLBI · UNIVERSITY OF ARIZONA · PI BLACK, STEPHEN M, FINEMAN, JEFFREY R · 2017 to 2020
$2.7M
Preclinical development of a novel Nrf2-activator formulation for the treatment of idiopathic pulmonary fibrosisR21AG054766 · NIA · UNIVERSITY OF ARIZONA · PI HECKER, LOUISE, MANSOUR, HEIDI M. · 2017 to 2018
$415k
Developing a Nrf2 activator for the treatment of COPDR41HL122004 · NHLBI · CUREVEDA, LLC · PI ALLAWAY, GRAHAM P · 2014 to 2014
$225k
Developing a Nrf2 activator for the treatment of sclerodermaR41AR066418 · NIAMS · CUREVEDA, LLC · PI ALLAWAY, GRAHAM P · 2014 to 2014
$225k
Development of small molecules targeting Nrf2 pathway for treatment of ColitisR43DK098984 · NIDDK · CUREVEDA, LLC · PI ALLAWAY, GRAHAM P · 2013 to 2013
$150k
NHLBI NIH HHS R01 HL137282NHLBI NIH HHS R41 HL122004NIAMS NIH HHS R41 AR066418NIA NIH HHS R21 AG054766NIDDK NIH HHS R43 DK098984NIH HHS HHSN2272201000033I/HHSN27200002 A65NIH HHS R41HL122004
6 · The paper itself

Abstract

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.

Indexed as

Acute Lung InjuryAdministration, InhalationCalorimetry, Differential ScanningCell LineDrug DiscoveryDry Powder InhalersHumansMicroscopy, ConfocalMicroscopy, Electron, ScanningNF-E2-Related Factor 2Particle SizePulmonary FibrosisRespiratory Distress SyndromeSpectrometry, X-Ray EmissionSpectroscopy, Fourier Transform InfraredTransition TemperatureNF-E2-Related Factor 2

Identifiers

PMID33188247
PMCPMC7666129
OpenAlexW3098624861

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.