Dry powder inhalers in COPD, lung inflammation and pulmonary infections

Muralidharan, Priya; Hayes, Don; Mansour, Heidi M.

doi:10.1517/17425247.2015.977783

Cited by 73 publications

(82 citation statements)

References 92 publications

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“…The pathophysiology of COPD 1 involves chronic inflammation of the airways due to chronic bronchitis and emphysema. Alveolar macrophages play a key role in this inflammatory response by releasing inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-IL 6, interleukin IL-8, monocyte chemotactic peptide (MCP)-1, leukotriene LTB4 and reactive oxygen species 2 .…”

Section: Introductionmentioning

confidence: 99%

Microparticulate/nanoparticulate powders of a novel Nrf2 activator and an aerosol performance enhancer for pulmonary delivery targeting the lung Nrf2/Keap-1 pathway

Muralidharan

Hayes

Black

et al. 2016

Mol. Syst. Des. Eng.

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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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Section: Introductionmentioning

confidence: 99%

Microparticulate/nanoparticulate powders of a novel Nrf2 activator and an aerosol performance enhancer for pulmonary delivery targeting the lung Nrf2/Keap-1 pathway

Muralidharan

Hayes

Black

et al. 2016

Mol. Syst. Des. Eng.

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“…7 Inhaled therapy via nebulization of antibiotic solution has become popular in the clinic for the treatment of respiratory infections. 8 Compared to wet nebulization, dry powder inhalers (DPIs) are gaining increasing interest for inhaled antibiotic treatment because in general powders are more stable than the wet formulations, provide access to higher dose in a single actuation 9 and DPIs are more convenient to carry; 10,11 although local side effects may occur due to inhaling high-dose powders of some drugs. 5 …”

Section: Introductionmentioning

confidence: 99%

Investigation of the Changes in Aerosolization Behavior Between the Jet-Milled and Spray-Dried Colistin Powders Through Surface Energy Characterization

Jong

Morton

et al. 2016

Journal of Pharmaceutical Sciences

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This study aimed to investigate the surface energy factors behind improved aerosolization performance of spray-dried colistin powder formulations compared to those produced by jet-milling. Inhalable colistin powder formulations were produced by jet-milling or spray-drying (with or without L-leucine). Scanning electron micrographs showed the jet-milled particles had irregularly angular shapes, while the spray-dried particles were more spherical. Significantly higher fine particle fractions (FPFs) were measured for the spray-dried (43.8-49.6%) vs. the jet-milled formulation (28.4 %) from a Rotahaler at 60L/min; albeit the size distribution of the jet-milled powder was smaller. Surprisingly, addition of L-leucine in the spray drying feed-solution gave no significant improvement in FPF. As measured by inverse gas chromatography, spray-dried formulations had significantly (p<0.001) lower dispersive, specific and total surface energy values and more uniform surface energy distributions than the jet-milled powder. Interestingly, no significant difference was measured in the specific and total surface energy values between the spray-dried formulation with or without L-leucine. Based upon our previous findings in the self-assembling behavior of colistin in aqueous solution and the surface energy data obtained here, we propose the self-assembly of colistin molecules during spray-drying, contributed significantly to the reduction of surface free energy and the superior aerosolization performance.

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“…In addition, efficient pulmonary drug delivery has been mostly achieved through specific devices and particle engineering technologies [52]. The face of the future in CF lung therapy is the development of easy to use dry powder for inhalation [53]. In this context, biocompatible nanoparticles, such as chitosan nanoparticles, are very suitable candidates because they permit an efficient protection of the gene material and its delivery to airway epithelial cells.…”

Section: Future Aspects: Clinical Application/dosage Formmentioning

confidence: 99%

Optimization of CFTR-mRNA transfection in human nasal epithelial cells

et al. 2016

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Background: Cystic fibrosis (CF) is the most common life-threatening inherited disease in the Caucasian population. It is caused by genetic defects in the cystic fibrosis transmembrane conductance regulator gene (CFTR), a cAMP regulated chloride-bicarbonate channel mainly located in the apical membrane of polarized epithelial cells. CFTR is proposed to regulate other proteins, including the epithelial sodium channel (ENaC). Recently, we successfully restored chloride current in CFTR deficient human airway epithelial cells using wtCFTR-mRNA transfection compared to non-CF cells showing similar values. The present study aimed to optimize the wtCFTR-mRNA transfection procedures in primary cultured human nasal epithelial (HNE) cells. Methods: Dose and time dependence experiments were performed. In addition, we investigated the possible impact of the wtCFTR-mRNA transfection on ENaC function in transepithelial measurements. We reduced the wtCFTR-mRNA dose stepwise and determined the minimal concentration of 0.6 μg/cm

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Dry powder inhalers in COPD, lung inflammation and pulmonary infections

Cited by 73 publications

References 92 publications

Microparticulate/nanoparticulate powders of a novel Nrf2 activator and an aerosol performance enhancer for pulmonary delivery targeting the lung Nrf2/Keap-1 pathway

Microparticulate/nanoparticulate powders of a novel Nrf2 activator and an aerosol performance enhancer for pulmonary delivery targeting the lung Nrf2/Keap-1 pathway

Investigation of the Changes in Aerosolization Behavior Between the Jet-Milled and Spray-Dried Colistin Powders Through Surface Energy Characterization

Optimization of CFTR-mRNA transfection in human nasal epithelial cells

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