Multi-organ Microfluidic Platform with Breathable Lung Chamber for Inhalation or Intravenous Drug Screening and Development

Efficient and economical delivery of pharmaceuticals to patients is critical for effective therapy. Here we describe a multiorgan (lung, liver and breast cancer) microphysiological system (“Body-on-a-Chip”) designed to mimic both inhalation therapy and/or intravenous therapy using curcumin as a model drug. This system is “pumpless” and self-contained using a rocker platform for fluid (blood surrogate) bidirectional recirculation. Our lung chamber is constructed to maintain an air-liquid interface and contained a “breathable” component that was designed to mimic breathing by simulating gas exchange, contraction and expansion of the “lung” using a reciprocating pump. Three cell lines were used: A549 for the lung, HepG2 C3A for the liver, and MDA MB231 for breast cancer. All cell lines were maintained with high viability (>85%) in the device for at least 48 hours. Curcumin is used to treat breast cancer and this allowed us to compare inhalation delivery versus intravenous delivery of the drug in terms of effectiveness and potentially toxicity. Inhalation therapy could be potentially applied at home by the patient while intravenous therapy would need to be applied in a clinical setting. Inhalation therapy would be more economical and allow more frequent dosing with a potentially lower level of drug. For 24 hour exposure to 2.5 and 25 μM curcumin in the flow device the effect on lung and liver viability was small to insignificant, while there was a significant decrease in viability of the breast cancer (to 69% at 2.5 μM and 51% at 25 μM). Intravenous delivery also selectively decreased breast cancer viability (to 88% at 2.5 μM and 79% at 25 μM) but was less effective than inhalation therapy. The response in the static device controls was significantly reduced from that with recirculation demonstrating the effect of flow. These results demonstrate for the first time the feasibility of constructing a multiorgan microphysiological system with recirculating flow that incorporates a “breathable” lung module that maintains an air-liquid interface.