Mathematical Models Guide Microliter Doses of Drugs to Specific Pathological Sites in the Lungs

In order to treat lung diseases such as cystic fibrosis, bronchopneumonia, chronic obstructive pulmonary disease, and lung cancer, drugs are administered in a systemic fashion, either orally or by aerosol inhalation. Large amounts of the drug have to be given in order to achieve therapeutic levels at the pathological site, and these doses may cause adverse effects to other organs in the body.

Investigators at Columbia University (New York, NY, USA) reported in the August 31, 2015, online edition of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) that they had developed a method for the precise delivery of drugs to a designated area of the lungs, which would lower the required dosage and reduce unwanted side effects.

Their method utilized a soluble liquid plug of very small volume (less than one milliliter) that was instilled into the upper airways. Programmed air ventilation of the lungs was employed to push the plug into a more distal airway to achieve deposition of liquid film onto the lung epithelium at a precisely determined location. The plug volume and ventilation conditions were determined by mathematical modeling of plug transport in a tubular geometry.

The investigators used three different in vivo imaging methods to demonstrate the application of targeted liquid film deposition to the lungs of animals in a rat model system. These results suggests that instillation of microvolumes of liquid into a ventilated pulmonary airway could be an effective strategy to deliver exact doses of drugs to targeted pathologic regions of the lung, especially those inaccessible by bronchoscopy. Using this method increased the in situ efficacy of the drug while minimizing any systemic side effects.

"We envision that our micro-volume liquid instillation approach will enable predictable drug concentrations at the target site, reducing the amount of drug required for effective disease treatment with significantly reduced side effects," said senior author Dr. Gordana Vunjak-Novakovic, professor of biomedical engineering and of medical sciences at Columbia University. "We are fascinated by the opportunities that bioengineering approaches offer to more effectively treat lung disease. The lung is a hugely complex organ that has billions of cells within a hierarchically organized tissue that cannot be built from scratch. Four years ago, we started research of lung regeneration using stem cells and bioengineering methods. And we continue to work with our clinical colleagues to develop new treatment approaches for treating lung disease."

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