Antimicrobial peptide biological activity, delivery systems and clinical translation status and challenges

Antibiotic resistance is currently one of the most significant threats to global public health and safety. And studies have found that over the next 25 years, 39 million people will die directly and 169 million indirectly due to antibiotic-resistant diseases. Consequently, the development of new types of antimicrobial drugs is urgently needed. Antimicrobial peptides (AMPs) constitute an essential component of the innate immune response in all organisms. They exhibit a distinctive mechanism of action that endows them with a broad spectrum of biological activities, including antimicrobial, antibiofilm, antiviral, and anti-inflammatory effects. However, AMPs also present certain limitations, such as cytotoxicity, susceptibility to protein hydrolysis, and poor pharmacokinetic properties, which have impeded their clinical application. The development of delivery systems can address these challenges by modifying AMP delivery and enabling precise, controlled release at the site of infection or disease. This review offers a comprehensive analysis of the mechanisms of action and biological advantages of AMPs. and systematically evaluate how emerging drug delivery systems, such as nanoparticles and hydrogels, enhance the stability and bioavailability of AMPs, discussing both their strengths and limitations. Moreover, unlike previous reviews, this review highlight the most recent clinically approved AMP-based drugs and those currently in development, emphasizing the key challenges in translating these drugs into clinical practice. With these perspectives, it is hoped that this review will provide some insights into overcoming translational barriers and advancing AMPs drugs into clinical practice.