Drug delivery platforms for the inhalation of biologics

The aim of this work was to develop, optimise and characterise dry powder formulations containing different therapeutic biologics to deliver them to the lungs. The main goal was not only to formulate highly respirable powders through a spray drying particle engineering approach, but also to maintain the therapeutic biologic agent stable and active after its formulation and storage. The first part of this thesis was focused on the manipulation of lactic acid bacteria and their transformation in a powder for inhalation to test their antibacterial and anti-inflammatory activity. The optimisation of the formulation applying a design of experiments approach, led to obtain a powder in which the probiotic viability was maintained and that showed a high respirability (> 50% of particles had a size < 5 µm). In addition, the probiotic powder showed bactericidal activity on Pseudomonas aeruginosa, bacteriostatic activity on Staphylococcus aureus and anti-inflammatory activity, when tested in vitro on A549 cells. The second part of the thesis was focused on the inclusion of peptides with different targets in dry powder formulations. Firstly, LCB1 was formulated for a local administration to the lungs, with the goal of blocking coronavirus-induced lung infection. The powder obtained using trehalose and L-leucine as excipients showed a high fraction of powder with a size < 5 µm and 2 µm (58.6% and 31.3%, respectively) and maintained the ability of the peptide to neutralise the virus even after the in vivo administration in rats. The other two peptides, pramlintide and semaglutide, were intended for a systemic absorption, as they target metabolic diseases such as diabetes and obesity. After a screening of excipients and buffering agents selected to preserve the structure of the two peptides, spray-dried powders were obtained with high respirability (> 55%). Moreover, the powder containing pramlintide showed to be stable when stored at 25°C up to six months and the ability to reduce the animals’ body weight, when administered intratracheally in rats.