Non-invasive airway health assessment: Synchrotron imaging reveals effects of rehydrating treatments on mucociliary transit in-vivo

Donnelley, Martin; Morgan, Kaye S.; Siu, Karen Kit Wan; Farrow, Nigel; Stahr, Charlene S.; Boucher, Richard C.; Fouras, Andreas; Parsons, David

doi:10.1038/srep03689

Cited by 26 publications

(41 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, quantitative imaging of co‐localization of tumor associated macrophages with therapeutic 64 Cu‐labeled polyglucose nanoparticle in an orthotopic model of lung adenocarcinoma was accomplished via PET, in vivo confocal microscopy, and tissue‐cleared LSFM . PCXI has already been applied for ex vivo and in vivo studies on mucociliary transport of large microparticles or 5–100 µm fibers in the trachea or upper airways of animal models such as mice and pigs and for monitoring the delivery of liquids to murine lungs via nose or intubated cannula delivery . Moreover, several common bulk particulates (e.g., lead dust, quarry dust, glass beads, asbestos, and Galena with size ≥ 5 µm) were tracked in live animal trachea airways by PCXI, showing the high variability in particle movement during mucociliary transport .…”

Section: Discussionmentioning

confidence: 99%

Multimodal Precision Imaging of Pulmonary Nanoparticle Delivery in Mice: Dynamics of Application, Spatial Distribution, and Dosimetry

Yang

Gradl

Dierolf

et al. 2019

Small

Self Cite

View full text Add to dashboard Cite

Targeted delivery of nanomedicine/nanoparticles (NM/NPs) to the site of disease (e.g., the tumor or lung injury) is of vital importance for improved therapeutic efficacy. Multimodal imaging platforms provide powerful tools for monitoring delivery and tissue distribution of drugs and NM/NPs. This study introduces a preclinical imaging platform combining X-ray (two modes) and fluorescence imaging (three modes) techniques for timeresolved in vivo and spatially resolved ex vivo visualization of mouse lungs during pulmonary NP delivery. Liquid mixtures of iodine (contrast agent for X-ray) and/or (nano)particles (X-ray absorbing and/or fluorescent) are delivered to different regions of the lung via intratracheal instillation, nasal aspiration, and ventilator-assisted aerosol inhalation. It is demonstrated that in vivo propagation-based phase-contrast X-ray imaging elucidates the dynamic process of pulmonary NP delivery, while ex vivo fluorescence imaging (e.g., tissue-cleared light sheet fluorescence microscopy) reveals the quantitative 3D drug/particle distribution throughout the entire lung with cellular resolution. The novel and complementary information from this imaging platform unveils the dynamics and mechanisms of pulmonary NM/NP delivery and deposition for each of the delivery routes, which provides guidance on optimizing pulmonary delivery techniques and noveldesigned NM for targeting and efficacy.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.

show abstract

Section: Discussionmentioning

confidence: 99%

Multimodal Precision Imaging of Pulmonary Nanoparticle Delivery in Mice: Dynamics of Application, Spatial Distribution, and Dosimetry

Yang

Gradl

Dierolf

et al. 2019

Small

Self Cite

View full text Add to dashboard Cite

show abstract

“…Donnelley et al [97] measured the variability of in vivo fluid dose distribution in liquid doses delivered through the pulmonary system. The affect of airway hydrating therapies on mucociliary transport [98,99] has also recently been investigated using synchrotron phase contrast imaging.…”

Section: Propagation-based Phase-contrast Imagingmentioning

confidence: 99%

Imaging regional lung function: A critical tool for developing inhaled antimicrobial therapies

Dubsky

Fouras

2015

Advanced Drug Delivery Reviews

Self Cite

View full text Add to dashboard Cite

Alterations in regional lung function due to respiratory infection have a significant effect on the deposition of inhaled treatments. This has consequences for treatment effectiveness and hence recovery of lung function. In order to advance our understanding of respiratory infection and inhaled treatment delivery, we must develop imaging techniques that can provide regional functional measurements of the lung. In this review, we explore the role of functional imaging for the assessment of respiratory infection and development of inhaled treatments. We describe established and emerging functional lung imaging methods. The effect of infection on lung function is described, and the link between regional disease, function, and inhaled treatments is discussed. The potential for lung function imaging to provide unique insights into the functional consequences of infection, and its treatment, is also discussed.

show abstract

“…Mucociliary transport rates have also been studied in vivo in animals and human volunteers (Donnelley et al, 2014a, Bondesson et al, 2007). It is recognised that clearance velocity is altered by some inhaled drugs and may be reduced in disease (Donnelley et al, 2014b) and may also vary between species (Hoffman and Asgharian, 2003). A variety of methods for studying drug binding to mucus and particle diffusion in models of respiratory mucus have been developed and this is currently an active area of research (Giorgetti 2016;Griessinger et al 2015 ).…”

Section: Non-absorptive Clearancementioning

confidence: 99%

Advances in experimental and mechanistic computational models to understand pulmonary exposure to inhaled drugs

Bäckman

Arora

Couet

et al. 2018

European Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

Prediction of local exposure following inhalation of a locally acting pulmonary drug is central to the successful development of novel inhaled medicines, as well as generic equivalents. This work provides a comprehensive review of the state of the art with respect to multiscale computer models designed to provide a mechanistic prediction of local and systemic drug exposure following inhalation. The availability and quality of underpinning in vivo and in vitro data informing the computer based models is also considered. Mechanistic modelling of local exposure has the potential to speed up and improve the chances of successful inhaled API and product development. Although there are examples in the literature where this type of modelling has been used to understand and explain local and systemic exposure, there are two main barriers to more widespread use. There is a lack of generally recognised commercially available computational models that incorporate mechanistic modelling of regional lung particle deposition and drug disposition processes to simulate free tissue drug concentration. There is also a need for physiologically relevant, good quality experimental data to inform such modelling. For example, there are no standardized experimental methods to characterize the dissolution of solid drug in the lungs or measure airway permeability. Hence, the successful application of mechanistic computer models to understand local exposure after inhalation and support product development and regulatory applications hinges on: (i) establishing reliable, bio-relevant means to acquire experimental data, and (ii) developing proven mechanistic computer models that combine: a mechanistic model of aerosol deposition and post-deposition processes in physiologically-based pharmacokinetic models that predict free local tissue concentrations.

show abstract

Non-invasive airway health assessment: Synchrotron imaging reveals effects of rehydrating treatments on mucociliary transit in-vivo

Cited by 26 publications

References 27 publications

Multimodal Precision Imaging of Pulmonary Nanoparticle Delivery in Mice: Dynamics of Application, Spatial Distribution, and Dosimetry

Multimodal Precision Imaging of Pulmonary Nanoparticle Delivery in Mice: Dynamics of Application, Spatial Distribution, and Dosimetry

Imaging regional lung function: A critical tool for developing inhaled antimicrobial therapies

Advances in experimental and mechanistic computational models to understand pulmonary exposure to inhaled drugs

Contact Info

Product

Resources

About