Bacterial infections of the respiratory tract cause millions of deaths annually. Several diseases exist wherein (1)
bacterial infection is the main cause of disease (e.g.,
tuberculosis and
bacterial pneumonia), (2)
bacterial infection is a consequence of disease and worsens the disease prognosis (e.g.,
cystic fibrosis), and (3) bacteria-triggered
inflammation propagates the disease (e.g.,
chronic obstructive pulmonary disease). Current approaches to combat
infections generally include long and aggressive
antibiotic treatments, which challenge patient compliance, thereby making relapses common and contributing to the development of antibiotic resistance. Consequently, the proportion of
infections that cannot be treated with conventional
antibiotics is rapidly increasing, and novel
therapies are urgently needed. In this context,
antimicrobial peptides (AMPs) have received considerable attention as they may exhibit potent antimicrobial effects against
antibiotic-resistant bacterial strains but with modest toxicity. In addition, some AMPs suppress
inflammation and provide other host defense functions (motivating the alternative term
host defense peptides (HDPs)). However, the delivery of AMPs is complicated because they are large, positively charged, and amphiphilic. As a result of this,
AMP delivery systems have recently attracted attention. For airway
infections, the currently investigated delivery approaches range from
aerosols and dry powders to various self-assembly and nanoparticle carrier systems, as well as their combinations. In this paper, we discuss recent developments in the field, ranging from mechanistic mode-of-action studies to the application of these systems for combating
bacterial infections in the airways.