Delivery Of Antimicrobial Peptides Research Articles

A Comprehensive Review of Recent Research into the Effects of Antimicrobial Peptides on Biofilms-January 2020 to September 2023.

Microbial biofilm formation creates a persistent and resistant environment in which microorganisms can survive, contributing to antibiotic resistance and chronic inflammatory diseases. Increasingly, biofilms are caused by multi-drug resistant microorganisms, which, coupled with a diminishing supply of effective antibiotics, is driving the search for new antibiotic therapies. In this respect, antimicrobial peptides (AMPs) are short, hydrophobic, and amphipathic peptides that show activity against multidrug-resistant bacteria and biofilm formation. They also possess broad-spectrum activity and diverse mechanisms of action. In this comprehensive review, 150 publications (from January 2020 to September 2023) were collected and categorized using the search terms 'polypeptide antibiotic agent', 'antimicrobial peptide', and 'biofilm'. During this period, a wide range of natural and synthetic AMPs were studied, of which LL-37, polymyxin B, GH12, and Nisin were the most frequently cited. Furthermore, although many microbes were studied, Staphylococcus aureus and Pseudomonas aeruginosa were the most popular. Publications also considered AMP combinations and the potential role of AMP delivery systems in increasing the efficacy of AMPs, including nanoparticle delivery. Relatively few publications focused on AMP resistance. This comprehensive review informs and guides researchers about the latest developments in AMP research, presenting promising evidence of the role of AMPs as effective antimicrobial agents.

Self-assembling peptide hydrogel scaffold integrating stem cell-derived exosomes for infected bone defects

Infected bone defect (IBD) is a great challenge in orthopedics, which involves in bone loss and infection. Here, a self-assembling hydrogel scaffold (named AMP-RAD/EXO), integrating antimicrobial peptides(AMPs), RADA16 and BMSCs exosomes with an innovative strategy, is developed and applied in IBD treatment for sustained antimicrobial ability, accelerating osteoblasts proliferation and promoting bone regeneration. AMPs present an excellent ability to inhibit infection, RADA16 is a self-assembling peptide hydrogel for AMPs delivery, and BMSCs exosomes can promote the bone regeneration. The prepared AMP-RAD/EXO exhibited a polyporous 3D structure for imbibition of BMSCs exosomes and migration of osteoblasts. In vitro studies indicate AMP-RAD/EXO can inhibit the growth of Staphylococcus aureus, accelerate the proliferation and migration of BMSCs. More importantly, in vivo results also prove that AMP-RAD/EXO exhibit an excellent effect on IBD treatment. Thus, the prepared AMP-RAD/EXO provides a multifunctional scaffold concept for bone tissue engineering technology.

Antimicrobial Peptide- and Dentin Matrix-Functionalized Hydrogel for Vital Pulp Therapy via Synergistic Bacteriostasis, Immunomodulation, and Dentinogenesis.

The preservation of vital pulps is crucial for maintaining the physiological functions of teeth; however, vital pulp therapy (VPT) of pulpitis teeth remains a substantial challenge due to uncontrolled infection, excessive inflammation, and limited regenerative potential. Current pulp capping agents have restricted effects in the infectious and inflammatory microenvironment. To address this, a multifunctional hydrogel (TGH/DM) with antibacterial, immunomodulatory, and mineralization-promoting effects is designed. The antimicrobial peptide (AMP) and demineralized dentin matrix are incorporated into the hydrogel, achieving sustainable delivery of AMP and a cocktail of growth factors. In vitro results show that TGH/DM could kill endodontic microbiota, ameliorate inflammatory responses of human dental pulp stem cells (hDPSCs), and prompt odontogenic differentiation of inflammatory hDPSCs via activation of peroxisome proliferator-activated receptor gamma. In vivo results suggest that TGH/DM is capable of inducing M2 phenotype transformation of macrophages in mice and fostering the regeneration of the dentin-pulp complex in inflamed pulps of beagle dogs. Overall, this study first proposes the synergistic regulation of AMP and tissue-specific extracellular matrix for the treatment of pulpitis, and the advanced hydrogel provides a facile and effective way for VPT.

The Two Dimensional Nanomaterials Functionalized with Antimicrobial Peptides as a Novel Strategy to Combat Biofilms and its Associated Infections

The resilient and adaptive nature of biofilms and its associated infections pose a serious threat in the current state of play aiming the need for a promising strategy. The two-dimensional nanomaterials functionalized with antimicrobial peptides serve as a novel approach to combat biofilms and their related infections. This review article explains the current landscape of research in this field focusing on classification and physiochemical properties of two-dimensional (2D) nanomaterials and their exploitation as antimicrobial peptide delivery system. The review also offers insights into their potential application in various settings such as medical devices wound healing and water treatment. Additionally we discuss the challenges and future directions in the development and implementation of this innovative strategy, emphasizing the need for multidisciplinary approach that bridges the gap between fundamental research and practical applications. Through a comprehensive synthesis of current literature, this review aims to provide researchers, clinicians and industry professionals with a thorough understanding of promises and challenges, which aim in the development of advanced materials and strategies for combating microbial biofilms and improving industrial control measures.

Advances in Transdermal Delivery of Antimicrobial Peptides for Wound Management: Biomaterial-Based Approaches and Future Perspectives

Advances in Transdermal Delivery of Antimicrobial Peptides for Wound Management: Biomaterial-Based Approaches and Future Perspectives

Efficient Delivery of Antimicrobial Peptides in an Innovative, Slow-Release Pharmacological Formulation.

Both nanostructure and multivalency enhance the biological activities of antimicrobial peptides (AMPs), whose mechanism of action is cooperative. In addition, the efficacy of a particular AMP should benefit from a steady concentration at the local place of action and, therefore, from a slow release after a dynamic repository. In the context of emerging multi-resistant bacterial infections and the urgent need for novel and effective antimicrobial drugs, we tested these concepts through the engineering of four AMPs into supramolecular complexes as pharmacological entities. For that purpose, GWH1, T22, Pt5, and PaD, produced as GFP or human nidogen-based His-tagged fusion proteins, were engineered as self-assembling oligomeric nanoparticles ranging from 10 to 70 nm and further packaged into nanoparticle-leaking submicron granules. Since these materials slowly release functional nanoparticles during their time-sustained unpacking, they are suitable for use as drug depots in vivo. In this context, a particular AMP version (GWH1-NIDO-H6) was selected for in vivo validation in a zebrafish model of a complex bacterial infection. The GWH1-NIDO-H6-secreting protein granules are protective in zebrafish against infection by the multi-resistant bacterium Stenotrophomonas maltophilia, proving the potential of innovative formulations based on nanostructured and slowly released recombinant AMPs in the fight against bacterial infections.

Self-Entrapment of Antimicrobial Peptides in Silica Particles for Stable and Effective Antimicrobial Peptide Delivery System.

Antimicrobial peptides (AMPs) have emerged as a promising solution to tackle bacterial infections and combat antibiotic resistance. However, their vulnerability to protease degradation and toxicity towards mammalian cells has hindered their clinical application. To overcome these challenges, our study aims to develop a method to enhance the stability and safety of AMPs applicable to effective drug-device combination products. The KR12 antimicrobial peptide was chosen, and in order to further enhance its delivery and efficacy the human immunodeficiency virus TAT protein-derived cell-penetrating peptide (CPP) was fused to form CPP-KR12. A new product, CPP-KR12@Si, was developed by forming silica particles with self-entrapped CPP-KR12 peptide using biomimetic silica precipitability because of its cationic nature. Peptide delivery from CPP-KR12@Si to bacteria and cells was observed at a slightly delivered rate, with improved stability against trypsin treatment and a reduction in cytotoxicity compared to CPP-KR12. Finally, the antimicrobial potential of the CPP-KR12@Si/bone graft substitute (BGS) combination product was demonstrated. CPP-KR12 is coated in the form of submicron-sized particles on the surface of the BGS. Self-entrapped AMP in silica nanoparticles is a safe and effective AMP delivery method that will be useful for developing a drug-device combination product for tissue regeneration.

Iron Oxide Nanoparticles with Supramolecular Ureido-Pyrimidinone Coating for Antimicrobial Peptide Delivery.

Antimicrobial peptides (AMPs) can kill bacteria by disrupting their cytoplasmic membrane, which reduces the tendency of antibacterial resistance compared to conventional antibiotics. Their possible toxicity to human cells, however, limits their applicability. The combination of magnetically controlled drug delivery and supramolecular engineering can help to reduce the dosage of AMPs, control the delivery, and improve their cytocompatibility. Lasioglossin III (LL) is a natural AMP form bee venom that is highly antimicrobial. Here, superparamagnetic iron oxide nanoparticles (IONs) with a supramolecular ureido-pyrimidinone (UPy) coating were investigated as a drug carrier for LL for a controlled delivery to a specific target. Binding to IONs can improve the antimicrobial activity of the peptide. Different transmission electron microscopy (TEM) techniques showed that the particles have a crystalline iron oxide core with a UPy shell and UPy fibers. Cytocompatibility and internalization experiments were carried out with two different cell types, phagocytic and nonphagocytic cells. The drug carrier system showed good cytocompatibility (>70%) with human kidney cells (HK-2) and concentration-dependent toxicity to macrophagic cells (THP-1). The particles were internalized by both cell types, giving them the potential for effective delivery of AMPs into mammalian cells. By self-assembly, the UPy-coated nanoparticles can bind UPy-functionalized LL (UPy-LL) highly efficiently (99%), leading to a drug loading of 0.68 g g-1. The binding of UPy-LL on the supramolecular nanoparticle system increased its antimicrobial activity against E. coli (MIC 3.53 µM to 1.77 µM) and improved its cytocompatible dosage for HK-2 cells from 5.40 µM to 10.6 µM. The system showed higher cytotoxicity (5.4 µM) to the macrophages. The high drug loading, efficient binding, enhanced antimicrobial behavior, and reduced cytotoxicity makes ION@UPy-NH2 an interesting drug carrier for AMPs. The combination with superparamagnetic IONs allows potential magnetically controlled drug delivery and reduced drug amount of the system to address intracellular infections or improve cancer treatment.

New Weapons to Fight against Staphylococcus aureus Skin Infections.

The treatment of Staphylococcus aureus skin and soft tissue infections faces several challenges, such as the increased incidence of antibiotic-resistant strains and the fact that the antibiotics available to treat methicillin-resistant S. aureus present low bioavailability, are not easily metabolized, and cause severe secondary effects. Moreover, besides the susceptibility pattern of the S. aureus isolates detected in vitro, during patient treatment, the antibiotics may never encounter the bacteria because S. aureus hides within biofilms or inside eukaryotic cells. In addition, vascular compromise as well as other comorbidities of the patient may impede proper arrival to the skin when the antibiotic is given parenterally. In this manuscript, we revise some of the more promising strategies to improve antibiotic sensitivity, bioavailability, and delivery, including the combination of antibiotics with bactericidal nanomaterials, chemical inhibitors, antisense oligonucleotides, and lytic enzymes, among others. In addition, alternative non-antibiotic-based experimental therapies, including the delivery of antimicrobial peptides, bioactive glass nanoparticles or nanocrystalline cellulose, phototherapies, and hyperthermia, are also reviewed.

Stimuli-Responsive Delivery of Antimicrobial Peptides Using Polyelectrolyte Complexes.

Antimicrobial peptides (AMPs) are antibiotics with the potential to address antimicrobial resistance. However, their translation to the clinic is hampered by issues such as off-target toxicity and low stability in biological media. Stimuli-responsive delivery from polyelectrolyte complexes offers a simple avenue to address these limitations, wherein delivery is triggered by changes occurring during microbial infection. The review first provides an overview of pH-responsive delivery, which exploits the intrinsic pH-responsive nature of polyelectrolytes as a mechanism to deliver these antimicrobials. The examples included illustrate the challenges faced when developing these systems, in particular balancing antimicrobial efficacy and stability, and the potential of this approach to prepare switchable surfaces or nanoparticles for intracellular delivery. The review subsequently highlights the use of other stimuli associated with microbial infection, such as the expression of degrading enzymes or changes in temperature. Polyelectrolyte complexes with dual stimuli-response based on pH and temperature are also discussed. Finally, the review presents a summary and an outlook of the challenges and opportunities faced by this field. This review is expected to encourage researchers to develop stimuli-responsive polyelectrolyte complexes that increase the stability of AMPs while providing targeted delivery, and thereby facilitate the translation of these antimicrobials.

Synthetic mucus biomaterials for antimicrobial peptide delivery.

Despite the promise of antimicrobial peptides (AMPs) as treatments for antibiotic-resistant infections, their therapeutic efficacy is limited due to the rapid degradation and low bioavailability of AMPs. To address this, we have developed and characterized a synthetic mucus (SM) biomaterial capable of delivering LL37 AMPs and enhancing their therapeutic effect. LL37 is an AMP that exhibits a wide range of antimicrobial activity against bacteria, including Pseudomonas aeruginosa. LL37 loaded SM hydrogels demonstrated controlled release with 70%-95% of loaded LL37 over 8 h due to charge-mediated interactions between mucins and LL37 AMPs. Compared to treatment with LL37 alone where antimicrobial activity was reduced after 3 h, LL37-SM hydrogels inhibited P. aeruginosa (PAO1) growth over 12 h. LL37-SM hydrogel treatment reduced PAO1 viability over 6 h whereas a rebound in bacterial growth was observed when treated with LL37 only. These data demonstrate LL37-SM hydrogels enhance antimicrobial activity by preserving LL37 AMP activity and bioavailability. Overall, this work establishes SM biomaterials as a platform for enhanced AMP delivery for antimicrobial applications.

Advances in Antimicrobial Peptide Discovery via Machine Learning and Delivery via Nanotechnology.

Antimicrobial peptides (AMPs) have been investigated for their potential use as an alternative to antibiotics due to the increased demand for new antimicrobial agents. AMPs, widely found in nature and obtained from microorganisms, have a broad range of antimicrobial protection, allowing them to be applied in the treatment of infections caused by various pathogenic microorganisms. Since these peptides are primarily cationic, they prefer anionic bacterial membranes due to electrostatic interactions. However, the applications of AMPs are currently limited owing to their hemolytic activity, poor bioavailability, degradation from proteolytic enzymes, and high-cost production. To overcome these limitations, nanotechnology has been used to improve AMP bioavailability, permeation across barriers, and/or protection against degradation. In addition, machine learning has been investigated due to its time-saving and cost-effective algorithms to predict AMPs. There are numerous databases available to train machine learning models. In this review, we focus on nanotechnology approaches for AMP delivery and advances in AMP design via machine learning. The AMP sources, classification, structures, antimicrobial mechanisms, their role in diseases, peptide engineering technologies, currently available databases, and machine learning techniques used to predict AMPs with minimal toxicity are discussed in detail.

Supramolecular Hydrogels for Precisely Controlled Antimicrobial Peptide Delivery for Diabetic Wound Healing

Diabetic wound patients are often exposed to bacterial infections with delayed healing process due to hyperglycemia in the damaged skin tissue. Antimicrobial peptides (AMPs) have been investigated for the treatment of infection-induced diabetic wounds, but their low stability and toxicity have limited their further applications to diabetic chronic wound healing. Here, we developed a precisely controlled AMP-releasing injectable hydrogel platform, which could respond to infection-related materials of matrix metalloproteinases (MMPs) and reactive oxygen species (ROS). The injectable supramolecular hydrogel was prepared by the simple mixing of hyaluronic acid modified with cyclodextrin (HA-CD) and adamantane (Ad-HA). Ad-HA was conjugated with AMP via the cyclic peptide linker composed of MMP and ROS cleavable sequence (Ad-HA-AMP). Remarkably, only when the AMP-tethered hydrogel was exposed to both MMP and ROS simultaneously, AMP was released from the hydrogel, enabling the controlled release of AMP without causing cytotoxicity. In addition, we confirmed the enhanced serum stability of the Ad-HA-AMP conjugate. The antimicrobial activity of Ad-HA-AMP was maintained much longer than that of the native AMP. Finally, we could demonstrate the greatly improved wound-healing effect of AMP-tethered hydrogels with enhanced safety for the treatment of infection-induced diabetic chronic wounds. Taken together, we successfully demonstrated the feasibility of sHG-AMP for diabetic chronic wound healing.

Advances of Antimicrobial Peptide-Based Biomaterials for the Treatment of Bacterial Infections.

Owing to the increase in multidrug-resistant bacterial isolates in hospitals globally and the lack of truly effective antimicrobial agents, antibiotic resistant bacterial infections have increased substantially. There is thus an urgent need to develop new antimicrobial drugs and their related formulations. In recent years, natural antimicrobial peptides (AMPs), AMP optimization, self-assembled AMPs, AMP hydrogels, and biomaterial-assisted delivery of AMPs have shown great potential in the treatment of bacterial infections. In this review, it is focused on the development prospects and shortcomings of various AMP-based biomaterials for treating animal model infections, such as abdominal, skin, and eye infections. It is hoped that this review will inspire further innovations in the design of AMP-based biomaterials for the treatment of bacterial infections and accelerate their commercialization.

Rational Design of Hydrogels for Cationic Antimicrobial Peptide Delivery: A Molecular Modeling Approach.

In light of the growing bacterial resistance to antibiotics and in the absence of the development of new antimicrobial agents, numerous antimicrobial delivery systems over the past decades have been developed with the aim to provide new alternatives to the antimicrobial treatment of infections. However, there are few studies that focus on the development of a rational design that is accurate based on a set of theoretical-computational methods that permit the prediction and the understanding of hydrogels regarding their interaction with cationic antimicrobial peptides (cAMPs) as potential sustained and localized delivery nanoplatforms of cAMP. To this aim, we employed docking and Molecular Dynamics simulations (MDs) that allowed us to propose a rational selection of hydrogel candidates based on the propensity to form intermolecular interactions with two types of cAMPs (MP-L and NCP-3a). For the design of the hydrogels, specific building blocks were considered, named monomers (MN), co-monomers (CM), and cross-linkers (CL). These building blocks were ranked by considering the interaction with two peptides (MP-L and NCP-3a) as receptors. The better proposed hydrogel candidates were composed of MN3-CM7-CL1 and MN4-CM5-CL1 termed HG1 and HG2, respectively. The results obtained by MDs show that the biggest differences between the hydrogels are in the CM, where HG2 has two carboxylic acids that allow the forming of greater amounts of hydrogen bonds (HBs) and salt bridges (SBs) with both cAMPs. Therefore, using theoretical-computational methods allowed for the obtaining of the best virtual hydrogel candidates according to affinity with the specific cAMP. In conclusion, this study showed that HG2 is the better candidate for future in vitro or in vivo experiments due to its possible capacity as a depot system and its potential sustained and localized delivery system of cAMP.

Dendritic Nanogels Directed Dual-Encapsulation Topical Delivery System of Antimicrobial Peptides Targeting Skin Infections.

Antimicrobial peptides (AMPs) are promising antibacterial agents in the fight against multidrug resistant pathogens. However, their application to skin infections is limited by the absence of a realizable topical delivery strategy. Herein, a hybrid hierarchical delivery system for topical delivery of AMPs is accomplished through the incorporation of AMPs into dendritic nanogels (DNGs) and their subsequent embedding into poloxamer gel. The high level of control over the crosslink density and the number of chosen functionalities makes DNGs ideal capsules with tunable loading capacity for DPK-060, a human kininogen-derived AMP. Once embedded into the poloxamer gel, DPK-060 encapsulated in DNGs displays a slower release rate compared to those entrapped directly in the gels. In vitro EpiDerm Skin Irritation Tests show good biocompatibility, while MIC and time-kill curves reveal the potency of the peptide toward Staphylococcus aureus. Anti-infection tests on ex vivo pig skin and in vivo mouse infection models demonstrate that formulations with 0.5% and 1% AMPs significantly inhibit the growth of S. aureus. Similar outcomes are observed for an in vivo mouse surgical site infection model. Importantly, when normalizing the bacteria inhibition to released/free DPK-060 at the wound site, all formulations display superior efficacy compared to DPK-060 in solution.

Antimicrobial Peptides against Bacterial Pathogens: Innovative Delivery Nanosystems for Pharmaceutical Applications.

The introduction of antibiotics has revolutionized the treatment and prevention of microbial infections. However, the global spread of pathogens resistant to available antibiotics is a major concern. Recently, the WHO has updated the priority list of multidrug-resistant (MDR) species for which the discovery of new therapeutics is urgently needed. In this scenario, antimicrobial peptides (AMPs) are a new potential alternative to conventional antibiotics, as they show a low risk of developing antimicrobial resistance, thus preventing MDR bacterial infections. However, there are limitations and challenges related to the clinical impact of AMPs, as well as great scientific efforts to find solutions aimed at improving their biological activity, in vivo stability, and bioavailability by reducing the eventual toxicity. To overcome some of these issues, different types of nanoparticles (NPs) have been developed for AMP delivery over the last decades. In this review, we provide an update on recent nanosystems applied to AMPs, with special attention on their potential pharmaceutical applications for the treatment of bacterial infections. Among lipid nanomaterials, solid lipid NPs and lipid nanocapsules have been employed to enhance AMP solubility and protect peptides from proteolytic degradation. In addition, polymeric NPs, particularly nanogels, are able to help in reducing AMP toxicity and also increasing AMP loading. To boost AMP activity instead, mesoporous silica or gold NPs can be selected due to their easy surface functionalization. They have been also used as nanocarriers for different AMP combinations, thus synergistically potentiating their action against pathogens.

Therapeutic potential of antimicrobial peptides for treatment of wound infection.

Healing of cutaneous wounds is a fundamental process required to re-establish tissue integrity, repair skin barrier function, and restore skin homeostasis. Chronic wound infection, exacerbated by the growing development of resistance to conventional therapies, hinders the skin repair process and is a serious clinical problem affecting millions of people worldwide. In the past decade, the use of antimicrobial peptides (AMPs) has attracted increasing attention as a potential novel strategy for the treatment of chronic wound infections due to their unique multifaceted mechanisms of action, and AMPs have been demonstrated to function as potent host-defense molecules that can control microbial proliferation, modulate host-immune responses, and act as endogenous mediators of wound healing. To date over 3,200 AMPs have been discovered either from living organisms or through synthetic derivation, some of which have progressed to clinical trials for the treatment of burn and wound injuries. However, progress to routine clinical use has been hindered due to AMPs' susceptibility to wound and environmental factors including changes in pH, proteolysis, hydrolysis, oxidation, and photolysis. This review will discuss the latest research focused on the development and applications of AMPs for wound infections using the latest nanotechnological approaches to improve AMP delivery, and stability to present effective combinatorial treatment for clinical applications.

Recent insight into strategies for the design of antimicrobial peptides (AMPs)

With the increasing development of antibiotic resistance among key bacterial pathogens, there is an urgent need to discover novel classes of antibiotics. Although antimicrobial peptides (AMP) with their specific mode of action are considered major candidates for next-generation antibiotics, several challenges limit the use of these peptides for therapeutic applications. In a large body of research, the focus is given to different approaches to the chemical modification of AMPs and how these modifications may improve the stability, antibiotic activity, proteolytic activity and prevent the cytotoxicity and side effects of AMPs. On the other hand, another group of research investigates the delivery of AMPs via nanocarrier systems as strategies used to enhance stability, control the release of peptides and reduce adverse peptide-related side effects, as well as improve their anti-microbial activities. In the present article, we surveyed most recently published researches that provide us with good knowledge on structural features, mechanism of action, therapeutic aim, advantages and limitations, chemical modification approaches and carrying strategies of AMPs. Finally, according to Quality by Design, the most important potential effective factor and potential risk were mentioned in the development of AMP delivery systems.

Antimicrobial Peptides: From Design to Clinical Application.

Infection of multidrug-resistant (MDR) bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Enterobacteriaceae (CRE), and extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, brings public health issues and causes economic burden. Pathogenic bacteria develop several methods to resist antibiotic killing or inhibition, such as mutation of antibiotic function sites, activation of drug efflux pumps, and enzyme-mediated drug degradation. Antibiotic resistance components can be transferred between bacteria by mobile genetic elements including plasmids, transposons, and integrons, as well as bacteriophages. The development of antibiotic resistance limits the treatment options for bacterial infection, especially for MDR bacteria. Therefore, novel or alternative antibacterial agents are urgently needed. Antimicrobial peptides (AMPs) display multiple killing mechanisms against bacterial infections, including directly bactericidal activity and immunomodulatory function, as potential alternatives to antibiotics. In this review, the development of antibiotic resistance, the killing mechanisms of AMPs, and especially, the design, optimization, and delivery of AMPs are reviewed. Strategies such as structural change, amino acid substitution, conjugation with cell-penetration peptide, terminal acetylation and amidation, and encapsulation with nanoparticles will improve the antimicrobial efficacy, reduce toxicity, and accomplish local delivery of AMPs. In addition, clinical trials in AMP studies or applications of AMPs within the last five years were summarized. Overall, AMPs display diverse mechanisms of action against infection of pathogenic bacteria, and future research studies and clinical investigations will accelerate AMP application.