2021, Feb 8, ISAM Webinar: Human lung cell culture models for developing aerosol medicines

Next ISAM Webinar - February 8, 2021

Title: Human lung cell culture models for developing aerosol medicines against bacterial infections

Time: 8 am – 9 am (San Diego, CA); 11 am – 12 am (New York, NY); 5 pm – 6 pm (Paris, France)

ZOOM Webinar Link: https://zoom.us/j/99309369199

Presented by Claus-Michael Lehr

Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), and Saarland University, Department of Pharmacy, 66123 Saarbrücken, Germany

Infectious diseases are on the raise and increasing challenge to human health with mortality rates predicted too soon exceed those of cancer and other diseases. Regardless of the recent pandemic caused by Corona virus, the problem of antimicrobial resistance continuous to increase while the number of new antibiotics and even the number of companies engaging in those is decreasing. Besides the need for new targets and molecules for anti-infective compounds, such as e.g. pathoblockers, there is also a need to deliver those across biological barriers preventing access to the target site. In this context aerosol medicines and pulmonary drug delivery deserve particular attention.

The air-blood barrier of the lungs with its large size (>100m2) and very thin epithelium (1-2μm) is a most attractive site for both systemic as well as local drug delivery. To study the cellular interactions of drugs and nanoparticles after deposition in the deep lung, our group has pioneered human alveolar epithelial cell models, including primary cells and as cell lines (1,2). More recently, we are moving towards microfluidic devices and more complex co-cultures, allowing to mimic the air-blood-barrier also in state of inflammation and chronic infections by biofilm forming bacteria (3,4,5). In vitro studies on such systems suggest that some novel self-assembling nanocarriers (6), capable to co-deliver Tobramycin and modern PQSI may allow to significantly reduce the dose of the antibiotic for completely eradicating the bugs and thus to reduce the risk of inducing antimicrobial resistance.

References

1. Elbert, K. J. et al. Monolayers of human alveolar epithelial cells in primary culture for pulmonary absorption and transport studies. Pharm Res 16, 601–608 (1999).
2. Kuehn, A. et al. Human alveolar epithelial cells expressing tight junctions to model the air-blood barrier. ALTEX 33, 251–260 (2016).
3. Costa, A., et al. Triple co-culture of human alveolar epithelium, endothelium and macrophages for studying the interaction of nanocarriers with the air-blood barrier. ACTA BIOMATERIALIA 91, 235–247 (2019).
4. Artzy Schnirman, A. et al. Capturing the Onset of Bacterial Pulmonary Infection in Acini‐On‐Chips. Adv. Biosys. 3, 1900026 (2019).
5. Montefusco-Pereira, C. V. et al. P. aeruginosa Infected 3D Co-Culture of Bronchial Epithelial Cells and Macrophages at Air-Liquid Interface for Preclinical Evaluation of Anti-Infectives. JoVE (2020). doi:10.3791/61069
6. Ho, D.-K. et al. Squalenyl Hydrogen Sulfate Nanoparticles for Simultaneous Delivery of Tobramycin and an Alkylquinolone Quorum Sensing Inhibitor Enable the Eradication of P. aeruginosa Biofilm Infections. Angew. Chem. Int. Ed. Engl. 59, 10292–10296 (2020).