(556f) Human Breathing Lung-on-a Chip for Inhalation Drug Delivery

The pulmonary administration has been considered one of an alternative choices for drug delivery since it has some unique features comparing to traditional delivery methods. For example, the inhaled drugs can avoid passing the first-pass hepatic metabolism through human stomach and liver which may degrade the drug molecules, leading to the actual dose lower than the minimum effective dose. Currently, the characteristics of the aerosolized drug have been evaluated by using the testing models to simulate the deposition distribution of the inhaled drugs in the human lung (e.g. Anderson cascade impactor). However, with a lack of pulmonary morphology and lung breathing motion, the simulation results obtained from these testing models may lead to a poor estimation of drug delivery. To recapitulate the physiological features of human bronchioles and alveoli, we developed an anatomically inspired lung device emulating the 15 to 19 generation of the branched geometry of human lung to study aerosol distribution behaviors under different breathing conditions.

The design of breathing lung device is consist of bifurcating channels terminated with deformable alveoli. The device is composed of layers of acrylic, polyester (PET) and inflatable polydimethylsiloxane (PDMS) membranes that were pre-cut with a laser cutter followed by laminating with adhesive tapes. These circular alveolar sacs can deform in a 4s per cycle to spontaneously produce breathing flow. The breathing mechanism was generated by a pressure change in the surrounding water chambers, thus lead to deformation of the flexible PDMS membrane.

We later connected the breathing lung device to an exposure chamber to observe the aerosol distribution profile under various breathing models. The distribution profile was obtained by using ImageJ software to localize the fluorescein deposition in the different generation of branched bronchiolar networks and terminated alveolar sacs. Our experimental results suggest that important features of specific human lung region can be reconstructed and breathing motions of the lung can be tuned corresponding to the diseased lung conditions. The results also provide a conceptual framework of aerosol deposition pattern under various pulmonary breathing models. This testing model gives a new insight into the development of inhalation drug that can potentially understand not only the delivery mechanism of small molecules but also the delivery efficiency of aerosolized biopharmaceuticals.