Chronic respiratory diseases (CRDs) caused 4 million deaths worldwide in 2019. CRD treatments are often administered by inhalation in particulate formulations. However, mucociliary clearance (MCC) acts as an effective physical barrier preventing drugs from reaching the target cells. This mechanism relies on the beating of cilia on the bronchi surface, which allows the displacement of the overlying mucus layer. Inhaled drugs are thus trapped by the mucus and quickly evacuated from the airways.
The objective of the MuST project was to model the mechanism of MCC using a microfluidic chip, to assess drug penetration through the moving mucus and thus provide a screening platform for new drug formulations. Our main objective could be subdivided into three research objectives: 1) Develop an adequate synthetic mucus model; 2) Reproduce the mucociliary clearance mechanism on a microfluidic chip; 3) Screen innovative drug formulations using our chip.
In this project, we combined biophysics, physical chemistry, soft condensed matter, and nanomedicine expertise. The originality of our approach lies in 3 key aspects: 1) We aimed to develop a synthetic mucus model that reproduces all the properties of native human mucus; 2) We chose to design a non-cellular MCC model, which will provide an easy, quick, cheap, and reproducible alternative to cell-based MCC models; 3) We aimed to apply an original technique called differential dynamic microscopy (DDM) to characterize the drug behaviour in the chip. DDM is perfectly adapted to measure particle diffusion in biological hydrogels under flowing conditions.
Our innovative screening platform should pave the way to design more efficient formulations to treat CRDs, with higher delivery rates, thereby improving the available treatments and lowering their costs. This project is in line with the United Nations’ aim “to reduce by 2030 by one-third premature mortality from non-communicable diseases [including CRDs] through prevention and treatment”.
