Inhalable dry powder formulations of the commercialised form of Deoxyribonuclease I - a dried alternative for the treatment of cystic fibrosis

Cystic fibrosis (CF) is an inherited condition characterised by thick mucus accumulation in the lungs, leading to recurrent pulmonary infections, inflammation and lung damage. Dornase alfa (Pulmozyme®), or recombinant human deoxyribonuclease I (rhDNase), is a mucolytic agent commonly used to decrease mucus viscosity and improve the lung function of CF patients. However, its delivery via nebulisation presents notable limitations: the process is time-intensive, requires refrigeration, and must be performed in a stationary setting-factors that collectively contribute to a high treatment burden and often reduced patient adherence. Inhalable dry powder formulations offer a promising alternative, combining portability, improved stability, and ease of use. This study explores the feasibility of converting commercially available rhDNase for nebulisation into a dry powder formulation, using bovine DNase I as a model system. Co-spray drying of bovine DNase I with sodium chloride and calcium chloride dihydrate was performed at a mass ratio of 1:8.77:0.15. A quality-by-design approach, utilizing a 2³ full-factorial design of experiments, was employed to assess the effects of critical process parameters - solution flow rate, atomising air flow rate, and outlet temperature - on quality attributes, including particle size distribution, yield, and protein recovery. The resulting spray-dried powders demonstrated suitable in vitro aerosolization characteristics suitable for pulmonary delivery, with enzymatic activity retention of up to 94%. In vitro tests on the most promising formulation showed no cell toxicity, supporting its potential for pulmonary delivery, as a patient-friendly alternative for CF therapy.