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Mazurkiewicz-Pisarek, A.; Baran, J.; Ciach, T. Applications of Antimicrobial Peptide. Encyclopedia. Available online: https://encyclopedia.pub/entry/44729 (accessed on 27 July 2024).
Mazurkiewicz-Pisarek A, Baran J, Ciach T. Applications of Antimicrobial Peptide. Encyclopedia. Available at: https://encyclopedia.pub/entry/44729. Accessed July 27, 2024.
Mazurkiewicz-Pisarek, Anna, Joanna Baran, Tomasz Ciach. "Applications of Antimicrobial Peptide" Encyclopedia, https://encyclopedia.pub/entry/44729 (accessed July 27, 2024).
Mazurkiewicz-Pisarek, A., Baran, J., & Ciach, T. (2023, May 23). Applications of Antimicrobial Peptide. In Encyclopedia. https://encyclopedia.pub/entry/44729
Mazurkiewicz-Pisarek, Anna, et al. "Applications of Antimicrobial Peptide." Encyclopedia. Web. 23 May, 2023.
Applications of Antimicrobial Peptide
Edit

Antimicrobial peptides (AMPs), or host defence peptides, are short proteins in various life forms. AMPs may become a promising substitute or adjuvant in pharmaceutical, biomedical, and cosmeceutical uses. Their pharmacological potential has been investigated intensively, especially as antibacterial and antifungal drugs and as promising antiviral and anticancer agents. AMPs exhibit many properties, and some of these have attracted the attention of the cosmetic industry. AMPs are being developed as novel antibiotics to combat multidrug-resistant pathogens and as potential treatments for various diseases, including cancer, inflammatory disorders, and viral infections. In biomedicine, AMPs are being developed as wound-healing agents because they promote cell growth and tissue repair. The immunomodulatory effects of AMPs could be helpful in the treatment of autoimmune diseases. 

antimicrobial peptides biofilm disruption drug development healthcare immunomodulatory effects

1. Introduction

AMPs with broad-spectrum antibacterial, antiviral, antifungal and anticancer activity are expected to become alternative antibiotics through the development of AMP-based therapies. Currently, several AMPs have been approved for antibacterial treatment by the Food and Drug Administration (FDA), and other AMPs are under clinical development [1]. Despite the promising potential of AMPs as medical therapeutics, there are many challenges that need to be overcome. The limitations to the intravenous administration of AMPs are caused by enzymatic degradation in blood plasma due to a short half-life. Oral application is also limited due to the pre-systemic enzymatic degradation of the peptides and poor penetration into the intestinal mucosa. In clinical trials, AMPs are mainly limited to topical applications due to their different enzymatic degradation, systemic toxicity and rapid hepatic and renal clearance [2][3]. Consequently, the local application of AMPs is the most common administration route, including delivery via topical dermal creams and skin softeners. In order to improve the AMP delivery system, polymeric materials such as hydrogels [4], chitosan [5], and hyaluronic acid [6] are used. AMPs may be covalently linked or non-covalently encapsulated in delivery systems. The covalent attachment of polyethylene glycol in a biomolecule (PEGylation) can reduce non-specific tissue uptake, cellular toxicity, and increase blood half-life and proteolytic degradation [7][8]. The conjugation of AMPs to hyperbranched polyglycerol (HPG) provides a better antimicrobial effect [9]. Lipids and surfactants can also be used as a conjugate to protect the peptides under extreme alkaline/acidic conditions and elevated temperatures [10]. Mesoporous silica particles [11], quantum dots [12], gold and silver nanoparticles [13][14], titanium [15], graphene [16] and carbon nanotubes [17] have also been used.
The high cost of peptide production also limits the commercial and clinical development of AMPs. The cost can be reduced by obtaining recombinant AMPs in prokaryotic or yeast expression systems with the usage of genetic engineering methods.

2. Pharmaceutical Applications

AMPs have several potential pharmaceutical applications due to their ability to kill or inhibit the growth of pathogens. Some AMPs have been found to be effective against Gram-negative and Gram-positive bacteria, including multidrug-resistant strains. They can also prevent the formation of bacterial biofilms, which are a common cause of chronic infections. Some AMPs have shown promise in treating fungal infections, with special emphasis on immunocompromised patients, such as those with HIV/AIDS. AMPs may work as antiviral drugs by disrupting viral entry, inhibiting viral replication, or promoting immune responses. The studies show that AMPs can work profitably with chemotherapy drugs. Some of them exhibit anticancer properties by inhibiting the growth and proliferation of cancer cells. AMPs have been shown to promote wound healing by accelerating the formation of new blood vessels and the migration of skin cells to the wound site. Moreover, they can be used as vaccine adjuvants and as natural preservatives [18].

2.1. Antibacterial Activity

The skin infection segment held the largest revenue share of 30.3% in 2021 and is likely to dominate the market during the forecast period. The growth of the skin infection segment is augmented by the rising prevalence of skin infections such as cellulitis, impetigo, furuncles, carbuncles, and others, and the wide availability of products for the treatment of bacterial skin infections. For instance, CUBICIN RF (daptomycin for injection), a type of lipopeptide product manufactured by Merck & Co., Inc., is used for the treatment of paediatric patients and adults with complicated skin and skin structure infections caused by Streptococcus aureus, Streptococcus pyogenes, and Streptococcus agalactia [19]. Daptomycin’s t½ is relatively long (~9 h), which allows once daily dosing in patients. This compound’s maximum dose ranges from 6 mg/kg up to 8 mg/kg, in which the linear pharmacokinetics is maintained up to 6 mg/kg.
However, the bloodstream infection segment is anticipated to register the fastest growth rate during the forecast period. The growth of this segment is augmented by the rising incidences of bloodstream infections, rising awareness about bloodstream infections, and the availability of a robust product portfolio for the management of bloodstream infections. For instance, Polymyxin B vials containing 500,000 units/vial manufactured by Xellia PHARMACEUTICALS are used for the treatment of bloodstream infections due to strains such as E. coli, Pseudomonas aeruginosa, and H. influenza [20][21].
Vancomycin and bacitracin are both antibiotics that are common AMPs from natural sources interfering with Gram-positive bacteria cell wall synthesis [22][23]. Vancomycin has been in clinical use since the 1950s and is approved for use in many countries worldwide under various brand names, including Vancocin, Vancomycin Hydrochloride, and others. It can be administered as an intravenous injection (15 to 20 mg/kg every 8 to 12 h), a capsule (125 to 500 mg four times daily), or in the case of skin infections, as a topical formulation (concentrations in the range of 1–2%) [24][25][26]. Bacitracin vials manufactured by Xellia Pharmaceuticals are indicated for the treatment of infants with pneumonia and empyema (50,000 units or 100,000 per ml of solution per vial). Bacitracin is an example of a polypeptide product that works by inhibiting bacterial cell wall synthesis. It is often used topically in ointments and creams [21][27][28]. Dalbavancin, primarily sold by Melinta Therapeutics, received FDA approval in May 2014. Since then, the drug has been marketed in the US and Europe. Sold under the brand name Dalvance/Allergan (500 mg/vial), Dalbavacin is used for treating acute bacterial skin and skin structure infections (dosage between 18 and 22.5 mg/kg with maximum 1500 mg) [29][30][31]. In 2018, Melinta reported global net product sales of $45,9 million for Dalvance [32]. It appears to be very effective in many serious Gram-positive infections. A long half-life and good diffusion in bone tissue suggest that Dalbavacin could be effective in the treatment of prosthetic joint infections. Even though AMPs are considered a cure for antibiotic-resistant bacteria, such as Staphylococcus aureus, some enterococci can gain resistance to this peptide, which is particularly concerning as they can cause serious infections that are difficult to treat [33]. Fortunately, some semi-synthetic peptide derivatives can be a solution in this case. Telavancin, sold by Theravance Biopharma, apart from skin infections, is also approved for the treatment of hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP; brand name Vibativ) [34]. Vibativ is indicated for skin infections and pneumonia, which share the same dosage of 10 mg/kg [35]. Similar to Vancomycin, Dalbavancin and Telavancin work by inhibiting bacterial cell wall synthesis. Oritavancin, another example of a semi-synthetic lipoglycopeptide, shares similar properties, but has a unique action mechanism. It can bind and disrupt bacterial cell membrane integrity, which is a beneficial antimicrobial property. It is FDA-approved for acute bacterial skin and skin structure infections under the brand name Orbactiv [36].
In September 2021, AuroMedics Pharma LLC announced that it received approval from USFDA to manufacture Daptomycin for an injection to treat serious bacterial infections, including skin and soft tissue infections, bloodstream infections, and endocarditis. Daptomycin is a lipopeptide antibiotic under the brand name Cubicin, administered intravenously (4 mg/kg) [37]. It works by disrupting the bacterial cell membrane. The same mechanism is shared by gramicidin, which is usually formulated in combination with other antibiotics. It is an antibiotic agent for the topical treatment of skin infections, with the drawback that the oral administration of this drug can be toxic. In vitro and in vivo studies have shown the great potential of this drug as a therapeutic agent in renal cell carcinoma, the most common type of kidney cancer in adults [38].
AMPs are reserved for use in situations where other antibiotics may not be effective. However, the use of antimicrobial peptides should be guided by susceptibility testing and other factors, similar to antibiotics, to minimise the risk the bacteria gaining resistance [39].

2.2. Antiviral Activity

Some AMPs have been shown to have antiviral activity against various viruses, including both enveloped and non-enveloped viruses [40]. There are nine peptidomimetic drugs on the market for the treatment of AIDS and at least four in clinical development for the treatment of HCV infections. Saquinavir, a peptidomimetic protease inhibitor, is a molecule with a hydroxy ethylene scaffold that mimics the typical peptide bond but is not broken down by HIV-1 protease. HIV (human immunodeficiency virus) is a target for antiviral peptides (AVPs) as they can be designed to target specific components of the virus, such as the fusion process and protease enzyme [40]. Enfuvirtide (T-20) is a synthetic peptide drug that is the first FDA-approved viral peptide inhibitor [41]. It is used for HIV infection and can be used to treat infections resistant to antiretroviral drugs HIV-1 derivative. The mechanism of action of Enfuvirtide is binding to glycoprotein 41 (gp41) in a way that prevents the conformational change required for fusion. As a result, this prevents the virus from entering the host cell and replicating. Enfuvirtide is administered by subcutaneous injections, which can lead to the frequent occurrence of painful injection site reactions. Hepatitis C is another viral infection that can be treated with antiviral peptides. Currently, two drugs are approved for that disease: a semi-synthetic peptide telaprevir and a synthetic peptide boceprevir [42]. They belong to a class of medications called protease inhibitors and have the same target. They block the replication of some types of hepatitis C viruses by targeting the NS3/4A protease enzyme, leading to the reduction of the virus in the blood, which results in improved liver function. These drugs are typically used in combination with PEGylated interferon and ribavirin. Since the COVID-19 outbreak, numerous antiviral peptides and peptidomimetics against SARS-CoV-2 have been reported. Although no peptide antiviral drugs for COVID-19 have entered clinical trials, some FDA-approved peptide drugs have been recommended for clinical trials for COVID-19 through virtual screenings and in silico drug repurposing methods. Researchers have shown that Enfuvirtide could inhibit SARS-CoV-2 entry into host cells with great potency and recommended it for COVID-19 clinical trials. Peptide-like small molecules, amino-acid-like derivatives, and peptidomimetics such as remdesivir and lopinavir have been utilised in COVID-19 clinical trials and treatment [43].

2.3. Anticancer Activity

Due to the resistance of cancer cells to treatment and the toxicity of cytostatics, new possibilities for anticancer therapies are constantly being sought. This has led the focus on AMPs, which have the ability to resist cancer growth. Zhao reported the anticancer activity of the HPRP-A1 peptide isolated from Helicobacter pylori [44]. Further, the combined effect of iRGD (homing peptide) and HPRP-A1 were examined for their enhancement of anticancer activity. Furthermore, the results suggested that iRGD helped to improve the penetration of HPRP-A1 into A549 MCS [45]. L-K6 was reported to be capable of killing MCF-7 breast cancer cells via nuclear disruption without cell surface disruption [46].

2.4. Broad Spectrum of Antimicrobial Activities

Despite promising results from preclinical and clinical studies, some AMPs require further work before being approved for pharmaceutical use. LL-37 is a naturally occurring AMP produced by immune cells, such as neutrophils and epithelial cells. Although it is not an FDA-approved drug, it has broad-spectrum activity, including in infectious diseases, inflammatory disorders, and cancer. LL-37 has several undesirable properties, such as possible bacterial resistance, cytotoxicity, and the inability to retain antimicrobial activity in the environment [47]. Clinical studies showed that LL-37 could be a potentially effective treatment option for patients with large ulcers [48]. Defensins are a family of small, cationic peptides found in various tissues and organs of the human body. They play a key role in the innate immune system by protecting against invading pathogens. They work by disrupting cell membranes, leading to cell lysis. In the review from 2019 on diabetic foot ulcers, it was suggested that beta-defensin-2 (hBD2) could be assessed as a drug for that disease [49]. Omiganan pentahydrochloride, a synthetic analogue of human defensin, was clinically tested for the treatment of atopic dermatitis, with significant results in reduction of the Scoring Atopic Dermatitis (SCORAD) index, showing it can be a safe and effective treatment option [50][51]. Nisin is a peptide produced by the bacteria Lactococcus lactis. Commonly used as a food preservative, it is now in clinical studies for bacterial infections. It works by membrane depolarisation, leading to the leakage of cellular contents and ultimately cell death. Clinical studies showed that nisin can be effective in the treatment of various bacterial infections, including diabetic foot ulcers and Helicobacter pylori infection [52][53][54]. Melittin is a naturally occurring peptide that is found in Apis mellifera venom. It has been studied for its therapeutic uses, including as an antimicrobial agent and as a potential cancer therapy [55][56]. Histatin-1 is a cationic peptide found in human saliva. It works by disrupting the cell membrane of microorganisms, causing cell lysis. It has been shown to be effective against a variety of oral pathogens, including Candida albicans, Streptococcus mutans, and Porphyromonas gingivalis [57][58]. Promising antimicrobial properties have been exhibited by pyocins derived from Pseudomonas aeruginosa. They have been successfully used in vivo in mice peritonitis treatment [39].
Obesity is a major health problem worldwide and is associated with numerous health risks, including type 2 diabetes. According to a report by Market Research Future, the obesity treatment market size is projected to grow over 31 Billion USD by 2030, showing a 16.70% compound annual growth rate (2023–2030) [59]. Inhibitors of pancreatic lipase activity are being investigated as potential treatments for obesity and related metabolic disorders. Several peptides isolated from soybean have demonstrated properties limiting the activity of that enzyme and are being considered for clinical trials [39].
Summing up, AMPs have various pharmaceutical applications, such as killing or inhibiting pathogen growth, preventing bacterial biofilms, treating fungal infections, working as antiviral drugs, and promoting wound healing. The market is dominated by the skin infection segment, while the bloodstream infection segment is projected to have the highest growth rate during the forecast period. Semi-synthetic peptide derivatives have been developed to address resistance issues; however, susceptibility testing should guide AMP use to minimise the risk of resistance.

3. Biomedical Applications

Modern healthcare uses various medical devices that improve or restore the function of the human body. This significantly improves the life quality of individuals affected by injuries or diseases [60] and generates demand for new technologies and special materials, which over the last decades have resulted in the development and popularisation of medical devices or biomaterials such as catheters [61], pacemakers [62], hip implants and prosthesis [63], and contact lenses [64]. All of these devices confer many benefits to patients but concurrently introduce the risk of microbial colonisation and infections due to foreign material being introduced to the body [65][66]

3.1. Implantable Devices

Medical treatments utilising various implants can cause infection by introducing microorganisms to the human body that are attached to the implantable devices, or the patients can be infected during hospitalisation [67][68]. Antibiotics are broadly used to protect patients from infection consequences that can be very serious; however, their overuse and improper use have caused the growth of antibiotic resistance [69][70]. Additional protection is provided by various coatings, a thin layer of material on the selected surface intended to improve its properties or create a protective layer against harmful factors [71], such as a shield against bacteria [72], fouling [73], UV light [74], and corrosive substances [75].
To prevent implantable devices from becoming infected, antimicrobial-releasing coatings are preferred, as the agent also reaches the peri-implant tissue [76]. Hydrogel-based AMPs proved to exhibit strong antimicrobial activity against Porphyromonas gingivalis, a major cause of peri-implantitis, with no signs of toxicity [77]. Additionally, a gelatine-based hydrogel deposited on Ti surfaces, which allows the controlled release of the short cationic AMP HHC36, is another example. AMP release prevented S. aureus, S. epidermidis, E. coli, and Pseudomonas aeruginosa biofilm formation [78]. The AMP HHC-36 sustained-release PDLLA-PLGA coating on TiO2 nanotubes maintained an effective drug release for 15 days in vitro and showed significant antiproliferative activity against Streptococcus aureus. In addition, in vivo studies demonstrated that the coating was biocompatible and antibacterial [79]. In another similar approach, GL13K-eluting coatings on TiO2 nanotubes prevented the growth of Fusobacterium nucleatum and Porphyromonas gingivalis [80]. A PCL-based dual coating proved the sustained antibacterial functionality of HHC36 for 14 days. The coating was translated onto silicone urinary catheters and showed promising antibacterial effectiveness when compared with the commercial silver-based Dover catheter [81]. Another scientific group modified PLA films by gallium implantation and subsequently functionalised them with hBD-1. Ga and defensin independently and synergistically contributed to the creation of a novel antimicrobial surface, which significantly decreased the total live bacterial biomass [82]. Melittin was physically stabilised on chitosan, chitosan/Vancomycin and oxacillin antibiotic coatings applied to etched Ti implants. The antimicrobial characteristics of the coatings and the synergistic effect of Melittin and antibiotics against MRSA and Vancomycin-resistant S. aureus (VRSA) were evaluated in two states: floating and adherent to the implant’s surface [83]. For orthopaedic and dental applications, a bioactive coating (Pac@PLGA MS/HA coated Ti) was deposited on the Ti surface Pac@PLGA MS/HA-coated Ti exhibited a cytotoxic effect on E. coli and S. aureus [84].

3.2. Biomedical Devices

The coatings can also enhance medical devices with multiple biofunctions such as drug delivery [85], biosensing [86], antibacterial properties [87], and osseointegration [88]. Devices with coatings can much better fulfil surgical and clinical requirements; therefore, the pharmaceutical and biomedical industries are constantly looking for advanced coatings with different functionalities. Many types of non-adhesive and antimicrobial coatings based on AMPs have been researched and tested [89][90]. These coatings can be divided into three groups: antifouling, contact-killing, and incorporating and releasing antimicrobials [91][92]. Chemical techniques are commonly used in contact-killing surfaces to immobilise AMPs to prevent microbial colonisation [93]. The structural properties of the peptides that are important for their antimicrobial activity should not be changed by the immobilisation process. Important parameters for AMP immobilisation include the orientation of the immobilised peptides and the AMP surface density, and the extent, flexibility, and spacer type for making the peptide–surface connection [94]. An example of a contact-killing surface is the hydrogel network with the covalently attached stabilised inverso-CysHHC10 peptide [95]. This coating exhibits antimicrobial activity in vitro against Streptococcus aureus, Streptococcus epidermidis, and E. coli. Additionally, brush-coating molecules may contain functional groups with antimicrobial activity, for example, through conjugation with the Tet20 [96] and Tet213 [97] AMPs. Another example is a polyurethane (PU) with a brush coating tethered to E6 AMP to avoid catheter-associated infection [98]. Chimeric peptide-modified Ti surfaces significantly reduced the adhesion of Streptococcus aureus, Streptococcus epidermidis, P. aeruginosa, and E. coli strains compared to bare Ti. Dental implants with immobilised GL13K on the Ti surface enabled osseointegration [99].

3.3. Multifunctional Coatings

The creation of multifunctional coatings by combining the arginylglycylaspartic acid (RGD) cell adhesion sequence with lactoferrin-derived LF1-11 resulted in cell integration in vitro and the inhibition of Streptococcus sanguinis colonisation [100]. Another study reported a self-assembling coating of recombinant spider silk protein combined with Magainin I, which had the effect of reducing the number of viable bacteria on the coated surfaces [101]. Furthermore, Magainin II, which was covalently bonded to stainless steel surfaces, showed antibacterial activity against strains of Streptococcus aureus and E. coli. The surface modified in this way reduced biofilm formation and the amount of bacteria on the stainless steel surface [102]. An example of antifouling surfaces is Tet20 and E6 being coupled to poly(DMA-co-APMA) copolymer brushes attached to polystyrene nanoparticles (NPs) by Yu et al. [97][103]. These AMP-functionalised coatings acted against P. aeruginosa and S. aureus, but the coatings were less operative than the sole AMPs in solution. Furthermore, Muszanska et al. created polymeric brushes by dip-coating AMP-functionalised block copolymer Pluronic F-127 onto a silicone rubber surface. The surfaces prevented Streptococcus aureus, Streptococcus epidermidis, and Pneumonia aeruginosa colonisation and killed surface-adhered bacteria [104].
Monteiro et al. conjugated the peptide Chain201D and EG4-SAM control peptide to carbonylimidazole-activated tetra(ethylene) glycol-terminated self-assembled monolayers (EG4-SAM) onto gold surfaces. Compared to the control peptide, Chain201D killed a high proportion of adherent S. aureus and E. coli [105]. Another interesting study is surface-functionalised PU (PU-DMH) comprising PDMAPS brushes as the lower layer and HHC36 peptide-conjugated poly(methacrylic acid) (PMAA) brushes as the upper layer. The PU-DMH surface exhibited bactericidal properties against E. coli and S. aureus bacteria, preventing the accumulation of bacterial debris on the surfaces. The functionalised surface possessed persistent antifouling and bactericidal activities, both under static and hydrodynamic conditions. The microbiological and histological results of animal experiments also verified its in vivo anti-infection performance [106].
Ti surfaces were coated by Acosta et al. with engineered protein (elastin-like recombinamers; ELR) containing D-GLI13K via silanisation [107]. The biofilm formation was reduced by 90% due to the presence of AMPs on the ELR coatings, and the viability of Streptococcus gordonii and Porphymonas gingivalis in the adherent population was significantly reduced. In a recent study, hydroxyapatite (HA) nanorods co-doped with Fe and Si were fabricated on a Ti surface. The AMP HHC-36 was chemically attached to nanorods with and without polymer brushes. The polymer-brush-grafted HHC-36 reduced >99.5% of Streptococcus aureus and E. coli bacterial strains. This activity was attributed to the collaborative effect of AMP and the physical puncturing by HA nanorods. The in vivo studies performed on HA nanorods with the polymer-brush-grafted HHC-36 showed a reduction in the inflammatory response and the inhibition of bacterial infection [81].

3.4. Water Purification Membranes

The shortage of clean drinking water has been a serious problem worldwide in recent years; therefore, the emerging application of polymer–bioactive molecule complexes has become a “hot” topic. Bacteria are present in almost every environment, especially in water, and antifouling membranes and surfaces have been prepared [108]. In this respect, composite membranes were synthesised by impregnating Ag NPs in the N-alkylated ter-polymer of poly(acrylonitrile), poly(n-butyl acrylate), and poly((2-dimethyl aminoethyl) methacrylate)), followed by cross-linking by the reaction with hydrazine hydrate. The antimicrobial activity of the composite membranes and a pristine membrane was determined by disc diffusion experiments on E. coli bacteria. The bacteria were drastically reduced (106 times) on the Ag-NP-containing membranes compared to the control [109].

3.5. Detection Biosensors

Detection biosensors are another area of AMP biomedical applications. Thionins are also used to develop biosensors for diabetics that detect glucose levels. Salimi and co-workers confirmed that thionin induced in multi-walled carbon nanotubes selectively detects glucose [110]. Another example is a lung cancer biomarker probe with a low detection limit. The biosensor was created using a graphene oxide–thionin–hemin–Au nanohybrid. In this case, graphene oxide acted as a supporting material in which thionin and hemin were immobilised, followed by a reduction of gold particles by thionin [111].

4. Cosmeceutical Applications

The increased worldwide demand for improving physical appearance, health and well-being is driving research studies intended to develop new cosmetics. The most commonly needed substances are for anti-ageing purposes such as the prevention or reduction of wrinkles and skin smoothing, but also improving skin tone or reducing whelk effects. To obtain such effects, modern cosmetics have to be capable of blocking ion channels, providing antioxidants and anti-inflammatory effects, reducing melanin synthesis or tyrosinase inhibition, inducing cell proliferation/renewal, and many others. According to the current knowledge, AMPs are able to provide such effects. Additionally, the topical application of AMPs is the most common administration route and is also mostly desired for cosmetic applications. This causes peptides to be attractive ingredients in science-based cosmetics and to play an important role in the cosmetic industry [112][113].
There are examples of promising trials of AMP applications in skin treatment. An AMP designated CopA3 was used to prevent the ultraviolet-induced inhibition of type I procollagen synthesis and inhibited the induction of matrix metalloproteinase-1 in human skin fibroblasts, showing the potential for antiwrinkle cosmetic ingredients [114]. Several studies showed the capacity of the peptide LL-37 to suppress excessive collagen synthesis, providing an antifibrogenic effect [115][116][117]. Other AMPs, such as IDR-1018 [118], SHARP1 [119], β-defensin-1, -2, -3 [120][121], human neutrophil peptide α-defensins (HNPs) [122], and DRGN-1 [123] have been successfully used for treating wounds and improving effective tissue regeneration without scarring.
Some AMPs have anti-inflammatory properties and can modulate the expression of cytokines, chemokines, and leukocyte activation [124]. Other AMPs such as indolicidin and its analogues [125], MC1-1 [126], sibaCec [127], SET-M33 [128], temporin-1TI and its analogues [129], hBD-3 [130][131][132], and LL-37 [133][134] have been shown to inhibit inflammatory responses. The peptides A3-APO successfully decreased the bacteria burden and reduced inflammation in acne [135]. The peptides (D4k) ascaphin-8 and (T5k) temporin-DRa were also effective at inhibiting the growth of Propionibacterium acnes, a pathogen resistant to the current antibiotics, and can be used to treat acne vulgaris [136]. Another positive effect was observed in modulating cellular renewal. AMPs have been shown to promote keratinocyte proliferation, including LL-37, which also promotes cellular migration and regenerative potential [137][138]. AMPs showing similar effect are IDR-1018 [139], PR-39 [140], human α-defensins (HNPs-1, -2, and -3) [141], human β-defensins [142][143][144], DAL-PEG-KSLW, KSLW [145], epinecidin-1 [146], psoriasin (s100a7) and koebnerisin (S100A15) [147]. Angiogenesis is an important aspect of skin appearance and health. Disorders of angiogenesis may cause rosacea, redness and vascular insufficiency [148].
Peptides such as AG-30/5C [149], LL-37 [137][150], PR-39 [151]; CRAMP [152], IDR-1018 [153], as well as α- and β-defensins [137] have the potential to counteract the age-induced decrease in angiogenesis in the skin and other tissues [142]. Peptide LfB17-34 can be used for skin whitening as it strongly increases melanin synthesis, which is associated with the elevated expression of the melanogenic enzymes tyrosinase and Trp1 [154].
Contributing factors to the ageing of the skin are reactive oxygen species. The intracellular formation of free radicals is influenced by ultraviolet light, ionising radiation, pollutants and diet [155]. Some peptides isolated from different fishes and mollusc species act as potential antioxidants [114][156][157][158][159][160][161]. Antioxidant activity was confirmed for several AMPs: temporin-TP1, brevinin-1TP1, brevinin-1TP2, brevinin-1TP3, brevinin-1LF1, palustrin-2GN1 [162].
The latest research studies of Unilever corporation patented in 2022 resulted in a novel and innovative approach. The external application of hydroxy stearic acid induced the secretion of AMPs from keratinocytes in the human body that act against bacteria infecting the skin, such as Streptococcus aureus and Pseudomonas aeruginosa [163].

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