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Inhaled Drug Delivery

Inhaled drug delivery is a crucial route for administering pharmaceuticals, particularly for respiratory conditions like asthma, chronic obstructive pulmonary disease (COPD), and infectious diseases. This route offers several advantages, including rapid onset of action, localized drug delivery to the affected areas of the respiratory system, and reduced systemic side effects. In preclinical research, inhaled drug delivery allows scientists to investigate the efficacy, safety, and pharmacokinetics of novel compounds, as well as to model and explore the mechanisms underlying respiratory disease.

SCIREQ offers turn-key solutions for advancing preclinical research in the field of inhaled drug delivery:

  • The inExpose system enables precise and controlled inhaled drug delivery, allowing researchers to replicate real-world inhalation scenarios accurately. This precision is essential for evaluating the pharmacokinetics and pharmacodynamics of inhaled medications, as well as for assessing their therapeutic efficacy.
  • The flexiVent system synchronizes inhaled dosimetry with ventilation, optimizing drug deposition and distribution in animal models, which is crucial for understanding the therapeutic potential of various drugs and formulations.
  • The expoCube system provides a controlled environment for the exposure of pulmonary tissues in vitro to diverse aerosols, allowing researchers to investigate the effects of different medications and environmental factors on lung tissues.

Related Products

  • Nebulized/resuspended drugs 
  • Lipid nanoparticles
  • Antisense oligonucleotides (ASO)
  • Small interfering RNA (siRNA)
  • Monoclonal antibodies
  • Vesicles/nanovesicles
  • Chitosan nanoparticles
  • Dry powders

Reproducible intervention, predictive outcomes

The administration of drugs or novel therapeutic carriers through the lung could be desirable for many reasons. The large surface area and high vascularization of the lung can provide a fast and effective delivery of substances either locally or systemically, via the blood. When considering inhalation as the route for drug delivery, SCIREQ’s intervention platform, the inExpose, offers a significant positive impact on study reproducibility and research efficiency by ensuring process standardization. Integrated with the Aeroneb nebulizer, the inExpose provides sophisticated computer control which enables automated, precise, and repeatable aerosol exposure sessions to small laboratory animals. Furthermore, the inExpose offers small internal volumes, reducing exposure ramp-up times and minimizing the need for large quantities of material.

References & Publications

Inhalation Delivery of Interferon-λ-Loaded Pulmonary Surfactant Nanoparticles Induces Rapid Antiviral Immune Responses in the Lung. (2024). Gil., C.H., et al. Applied Materials & Interfaces, https://doi.org/10.1021/acsami.3c13677

Serotonin-2 Receptor Agonists Produce Anti-inflammatory Effects through Functionally Selective Mechanisms That Involve the Suppression of Disease-Induced Arginase 1 Expression. (2024). Flanagan et al. ACS Pharmacology & Translational Science. https://doi.org/10.1021/acsptsci.3c00297

Inhaled delivery of recombinant interferon-lambda restores allergic inflammation after development of asthma by controlling Th2- and Th17-cell-mediated immune responses. (2022). Won, J., et al. International Immunopharmacology, 112: 109180

Aerosol delivery of ferulic acid-loaded nanostructured lipid carriers: A promising treatment approach against the respiratory disorders. (2017). Hassanzadeh, P., et al. Physiology & Pharmacology,21: 331-342

Formulation, Characterization and Pulmonary Deposition of Nebulized Celecoxib Encapsulated Nanostructured Lipid Carriers. (2010). Patlolla, R.R., et al. J Control Release, 144(2): 233-241

Nebulized Anti–IL-13 Monoclonal Antibody Fab′ Fragment Reduces Allergen-Induced Asthma. (2012). Hacha, J., et al. American Journal of Respiratory Cell and Molecular Biology, 47(5)

Pulmonary Biocompatibility Assessment of inhaled Single-wall and Multiwall Carbon Nanotubes in BALB/c Mice. Ravichandran, P. (2012). Journal of Biological Chemistry, doi: 10.1074/jbc.M111.251884

Efficacy of aerosol therapy of lung cancer correlates with EGFR paralysis induced by AvidinOX-anchored biotinylated Cetuximab. De Santis et al. Oncotarget. 2014 Aug;5(19):9239-55.

Lower respiratory tract delivery, airway clearance, and preclinical efficacy of inhaled GM-CSF in a postinfluenza pneumococcal pneumonia model. (2020). Umstead, T.M., et al. Lung Cellular and Molecular Physiology, https://doi.org/10.1152/ajplung.00296.2019

Exposure to atmospheric Ag, TiO2, Ti and SiO2 engineered nanoparticles modulates gut inflammatory response and microbiota in mice. (2022). Guilloteau, E., et al. 

Inhalation Delivery of Type III Interferons Restricts Epithelial-Derived Th2 Inflammation and Pathologic Responses in Allergic Asthma. Kim, H.J., et al (2019). Am J Respir Crit Care Med, 199: A2901

Particulate Matter Exposure Exacerbates Amyloid-β Plaque Deposition and Gliosis in APP/PS1 Mice. (2021). Bijayani, S., et al. Journal of Alzheimer’s Disease, 80(2): 761-774

The histone methyltransferase Ezh2 restrains macrophage inflammatory responses. (2021). Kitchen, G.B., et al. FASEB J, 35(10): e21843

Toxicity Assessment of 91-Day Repeated Inhalation Exposure to an Indoor School Air Mixture of PCBs. (2022). Wang., H et al. Environ. Sci. Technology. 56(3): 1780-1790

Biologically Relevant Murine Models of Chronic Pseudomonas aeruginosa Respiratory Infection. (2023). Rodgers, A.M., et al. Pathogens, 12(8) 1053; https://doi.org/10.3390/pathogens12081053

Role of nestin/14-3-3/mTOR signaling in airway smooth muscle cell proliferation and airway remodeling. (2023). Tang., D., et al. Nature Portfolio, https://doi.org/10.21203/rs.3.rs-2869821/v1

Acute in vivo pulmonary toxicity assessment of occupationally relevant particulate matter from a cellulose nanofiber board. (2020). Parizek, N., et al. NanoImpact, 17: 100210

Repetitive Sulfur Dioxide Exposure in Mice Models Post-Deployment Respiratory Syndrome. (2023). Gutor, S.S., et al. BioRxiv, doi: https://doi.org/10.1101/2023.05.15.540867

Time course of pulmonary inflammation and trace element biodistribution during and after sub-acute inhalation exposure to copper oxide nanoparticles in a murine model. (2022). Areecheewakul, S., et al. Particle and Fibre Toxicology, 40

SRC and TKS5 mediated podosome formation in fibroblasts promotes extracellular matrix invasion and pulmonary fibrosis. (2023). Barbayianni, I., et al. Nature Communications, 14: 5882

Abi1 mediates airway smooth muscle cell proliferation and airway remodeling via Jak2/STAT3 signaling. (2022). Wang, R., et al. iScience Cell Press, 25: 103833

Inhaled dosimetry

Ventilator Assisted Drug Delivery (VAAD) is a hybrid between nose-only inhalation and intratracheal instillation. The approach consists in intubating the subject and using optimized computer-controlled ventilation profiles to administer the inhaled compound deep into the subject’s lungs, over several breaths. This strategy minimizes subject-to-subject variability, and fosters a highly homogenous aerosol deposition within the lung. It further allows researchers to measure the lung function of the subject prior to and post administration. VAAD can therefore be used for drug delivery and disease modelling (e.g. for IPF studies with Bleomycin). 

References & Publications

Reliable and effective in vitro exposure

The expoCube is a novel Air Liquid Interface (ALI)/Transwell in vitro exposure system which permits highly reliable and effective deposition of aerosols onto cells and tissues. This exposure takes advantage of Thermophoresis, which guides small particles and gas onto the target tissue through a temperature gradient and increases the deposition rate from 2% to ~40%.

References & Publications

Developing Inhaled Cannabis Product Methods for in vitro Toxicological Assessment. Wilson, E., et al (2023). SOT 2023

56th Congress EUROTOX 2021, virtual congress, Copenhagen, Denmark “Can We Get The Full Picture? Comparison of a Series of Volatile Chemicals’ Action on Gene Expression in A549 Cells as Part of a Read-Across Approach. “ W. Zoblet al. (2021). 

A novel microfluidic platform for pulmonary nanoparticle exposure .Kiss, F.M et al. (2021). 11th edition of the World Congress on Alternatives and Animal Use in the Life Sciences, virtuel congress, Maastricht, Netherlands

“Intermittent exposure to whole cigarette smoke alters the differentiation of primary small airway epithelial cells in the air-liquid interface culture”, Gindele, J.A, et al. (2020). Scientific Reports volume 10, Article number: 6257

Cigarette smoke exposure disrupts epithelial barrier function and impairs antiviral immune response to influenza infection ex vivo. Böhlen, S. et al. (2020). Models of Lung Disease Workshop 2020, Hannover (Germany)

“Hazard assessment of diacetyl and structurally related diketones – a read-across approach”, Hansen, T., et al. (2020). EU-ToxRisk Symposium (2020), Egmont aan Zee (Netherlands), 

 “Development of alternative in vitro and ex vivo models for testing of inhalable antibiotics – InhalAb.”Wronski, S., et al. (2020). Models of Lung Disease Workshop 2020, Hannover (Germany),

“In vitro inhalation cytotoxicity testing of therapeutic nanosystems for pulmonary infection”. Ritter, D., et al. (2020). Journal of the European Society of Toxicology in Vitro “Toxicology in Vitro”, Volume 63, 2020, 

Resources

NEBS AND PIEZO2: GUARDIANS OF THE RESPIRATORY GALAXY

In a recent Nature publication by Schappe,M (2024), researchers have revealed a fascinating aspect of respiratory physiology: the role of sensory neurons in guarding against airway obstruction and orchestrating crucial reflexes to maintain respiratory function.

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SoftRestraints for Inhalation Exposure Studies

Any restraining device used in an inhalation exposure set-up will be, by definition, restricting the subject’s ability to move. SCIREQ’s SoftRestraints are designed to minimize some of these important effects typical restraints have on the subject.

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