Fundamental research on respiratory transport phenomena, and in particular approaches for pulmonary drug delivery, are overwhelmingly focused on efforts conducted in adults. Results are then typically translated (or scaled down) and adopted to children. Yet, children are not miniature adults: their distinct and developing lung structures and heterogeneous ventilation patterns set them aside from their parents. Whether concerned with inhalation aerosol therapies for topical delivery (e.g. asthma) or systemic delivery (e.g. vaccination), current methods and strategies for delivery face ongoing challenges with typically low yields in achieving optimal delivery of therapeutics (i.e. low deposition rates). Such delivery challenges are also true for liquid-based therapies such as surfactant replacement therapy (SRT) in treating pulmonary conditions of the newborn (e.g. infant respiratory distress syndrome).
To this day, the deposition of inhaled pharmaceutics in young children remains alarmingly low. While parents and the broader public may not be fully aware, the deposition efficiency of inhaled drugs in kids is typically less than 10% for a given dose. In particular, for diseases that require targeting deep alveolated airways (e.g. cystic fibrosis), lung deposition is further reduced to levels below 5%. In turn, low deposition efficiencies of inhaled aerosols often require treatments based on "flooding" the lungs with drugs to achieve sufficient drug deposition, and thus carrying the risk of local side effects including inflammation due to deposition “hot spots” and possible systemic side effects as a result of chronic drug therapy. In parallel to inhalation aerosols, liquid therapies are commonly instilled in premature babies suffering from infant respiratory distress syndrome (IRDS). Premature births (about 13 million births/year worldwide) contribute to >25% of global neonatal deaths and are often accompanied by a surfactant deficiency. Surfactant replacement therapy is the foremost strategy used to treat IRDS by instilling endotracheally a surfactant-laden bolus in the neonatal lungs. In many instances, however, the bolus has to be administered more than once to ensure reaching alveoli. Since data are frequently limited, the optimal method for surfactant delivery has yet to be proven.
RespMicroFlows sets out to radically revisit the challenges of pulmonary drug delivery in babies and young children. By developing advanced in silico numerical simulations together with in vitro platforms mimicking the respiratory airway environment, our efforts will not only deliver a gateway to reliably assess the outcomes of inhaling aerosols and predict deposition patterns in young populations, but furthermore we will unravel the fundamentals of liquid bolus transport to achieve optimal surfactant delivery strategies in premature neonates. By recreating cellular environments that capture underlying physiological functions, our advanced organ-on-chips will deliver both at true scale and in real time the first robust and reliable in vitro screening platforms of exogenous therapeutic materials in the context of inhaled aerosols and surfactant-laden installations. Combining advanced engineering-driven flow visualization solutions with strong foundations in transport phenomena, fluid dynamics and respiratory physiology, RespMicroFlows' ambitions are entrenched in delivering new paradigms in drug delivery
