Advancing portable, aqueous drug delivery to the human lung

Sammanfattning: Lung disease profoundly impacts human health: many lung diseases are currently without cure and require continued treatment. Due to their ease of use and integration into the daily routine, portable inhalers are the preferred treatment option for patients. Efforts to replace greenhouse-gas active portable inhalers have led to portable aqueous systems, so-called Soft mist inhalers (SMIs). However, compared to propellant-driven systems on the market, SMI aerosolization units still face drawbacks in their pathogenic safety, have a big silicon footprint, and must be manufactured in cleanroom environments. Three different types of spray nozzle were developed in this thesis, that improve upon the state of the art in pathogenic safety, fabrication cost, and aerosolization performance. For the first time, a novel 3D-printed, monolithic Swirl nozzle allows the fabrication of such an aerosolization unit outside a cleanroom environment. This device further enables the soft aerosolization of fragile and shear-sensitive large molecule pharmaceutics. A new approach to handling and packaging silicon MEMS allowed the demonstration of the world’s smallest aqueous spray nozzle for portable inhalers with a silicon footprint of just 1/6 of a square millimeter. Improving upon the lacking pathogenic safety of SMI devices, a valved spray nozzle was developed that effectively seals the inhalation unit at nozzle level against pathogenic ingrowth of motile enteric bacteria.These developments may enable environmentally friendly SMIs to improve the treatment of a broad range of lung diseases.