Nanostructured antimicrobial peptides: The last push towards clinics

Abstract Peptide drugs hold great potential for the treatment of infectious diseases due to their unconventional mechanisms of action, biocompatibility, biodegradability and ease of synthesis and modification. The increasing rising of bacterial strains resistant to classical antibiotics have pushed the development of new peptide-based antimicrobial therapies. In this context, over the past few years, different approaches have reached a clinical approval. Furthermore, the application of nanotechnological principles to the design of antimicrobial peptide-based composites increases even more the already known benefits of antimicrobial peptides as competent protein drugs. Then, we provide here an overview of the current strategies for antimicrobial peptide discovery and modification and the status of such peptides already under clinical development. In addition, we summarize the innovative formulation strategies for their application, focusing on the controlled self-assembly for the fabrication of antimicrobial nanostructures without the assistance of external nanocarriers, and with emphasis on bioengineering, design of ultra-short peptides and rising insights in bacterial selectivity.