Antimicrobial Peptides: A New Hope in Biomedical and Pharmaceutical Fields

Abstract

Antibiotics are essential drugs used to treat pathogenic bacteria, but their prolonged use contributes to the development and spread of drug-resistant microorganisms. Antibiotic resistance is a serious challenge and has led to the need for new alternative molecules less prone to bacterial resistance. Antimicrobial peptides (AMPs) have aroused great interest as potential next-generation antibiotics, since they are bioactive small proteins, naturally produced by all living organisms, and representing the first line of defense against fungi, viruses and bacteria. AMPs are commonly classified according to their sources, which are represented by microorganisms, plants and animals, as well as to their secondary structure, their biosynthesis and their mechanism of action. They find application in different fields such as agriculture, food industry and medicine, on which we focused our attention in this review. Particularly, we examined AMP potential applicability in wound healing, skin infections and metabolic syndrome, considering their ability to act as potential Angiotensin-Converting Enzyme I and pancreatic lipase inhibitory peptides as well as antioxidant peptides. Moreover, we argued about the pharmacokinetic and pharmacodynamic approaches to develop new antibiotics, the drug development strategies and the formulation approaches which need to be taken into account in developing clinically suitable AMP applications.

Keywords: antimicrobial peptides; biomedical and pharmacological applications; drug delivery; drug-resistant microorganisms; pharmacokinetics and pharmacodynamics.

Figure 1

(A) in aqueous solution, the AMPs are unstructured while after the interaction with biological membrane, particularly with the LPS component, they assume the right conformation, which can be (B) α-helical, β-sheet, mixed α-helical/β-sheet, and loop. Figure created with Biorender.com and UCSF CHIMERA software (Pettersen et al., 2004).

Figure 2

Antimicrobial peptides can act through a membranolytic and non-membranolytic mechanism. In the membranolytic mechanism AMPs can lead to (A) pore formation on the cell membrane or (B) micelle formation on the cell membrane. In the non-membranolytic mechanism, (C) AMPs can penetrate cell membranes and interact with intracellular targets, such as DNA and proteins. Figure created with Biorender.com and UCSF CHIMERA software (Pettersen et al., 2004).

Figure 3

Chemical and physical bonds to obtain hydrogels. Hydrogels can also be prepared by a hybrid interaction consisting of physical interactions and/or covalent bond formation, exhibiting at the same time reversible mechanical properties and long-term stability.

Figure 4

Cubosomes comprise curved lipid bilayers with a well-defined disposition and divided into two internal aqueous channels that can be exploited by antimicrobial peptides. Figure created with Biorender.com.

Figure 5

Arrangement of peptide amphiphiles in self-assembling nanostructures (e.g., micelles and microtubes), which can contain and release APIs. Adapted from Song et al. (2017). Figure created with UCSF CHIMERA software (Pettersen et al., 2004).