Background: Since the first isolation of antimicrobial peptides (AMPs) they
have attracted extensive interest in medicinal chemistry. However, only a few AMP-based
drugs are currently available on the market. Despite their effectiveness, biodegradability,
and versatile mode of action that is less likely to induce resistance compared to conventional
antibiotics, AMPs suffer from major issues that need to be addressed to broaden
their use. Notably, AMPs can lack selectivity leading to side effects and cytotoxicity, and
also exhibit in vivo instability. Several strategies are being actively considered to overcome
the limitations that restrain the success of AMPs.
Methods: In the current work, recent strategies reported for improving AMPs in the context
of drug design and delivery were surveyed, and also their possible impact on patients
and the environment was assessed.
Results: As a major advantage AMPs possess an easily tunable skeleton offering opportunities
to improve their properties. Strategic structural modifications and the beneficial
properties of cyclic or branched AMPs in term of stability have been reported. The conjugation
of AMPs with nanoparticles has also been explored to increase their in vivo stability.
Other techniques such as the coupling of AMPs with specific antibodies aim to increase
the selectivity of the potential drug towards the target. These strategies were evaluated
for their effect on the environment highlighting green technologies.
Conclusion: Although further research is needed taking into account both environmental
and human health consequences of novel AMPs, several of these compounds are promising
drug candidates for use in sustainable medicine.