Inhalable dry powders for chemically-modified human Cationic AntiMicrobial Peptides (CAMPs): moving toward in vivo application

Cationic Antimicrobial Peptides (CAMPs) are a valuable alternative to conventional antibiotics because they have broad spectrum antimicrobial activity and low ability to induce the onset of resistant strains. Even if the protein nature of CAMPs makes difficult their use as systemic agents they are ideally suited for direct delivery to airways and lung. The main aim of this project is to develop inhalable dry powders for lung‐delivery of human CAMPs and CAMP‐releasing proteins (CAMP‐RPs) carrying simple chemical modifications which improve their antimicrobial activity.A wide panel of human CAMPs and CAMP‐RPs will be prepared by recombinant DNA procedures and chemical synthesis, modified by means of a method already developed by the proponents and assayed on clinical P. aeruginosa strains to evaluate their bactericidal activity.Moreover during the design and development of the particles we will be considered crucial parameters for transferability in vivo (such as aerodynamic properties, resistance to proteases, and so on). The analysis of the interactions between CAMPs and acidic polysaccharides, such as alginate and hyaluronic acid, will allow to design rationally the inhalable particles.The final result will be a panel of inhalable dry powder formulations containing CAMP(-RP)s suited for direct lung-delivery and able to fight Pseudomonas infection.