Nanoparticles Encapsulated with LL37 and Serpin A1 Promotes Wound Healing and Synergistically Enhances Antibacterial Activity

Fumakia, Miral; Ho, Emmanuel A.

doi:10.1021/acs.molpharmaceut.6b00099

Cited by 106 publications

(60 citation statements)

References 74 publications

(103 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The data described so far indicate that the peptide SA1-III maintains the ability to increase collagen production previously described for the originator protein serpin A1 (Dabbagh et al, 2001;Fumakia and Ho, 2016) and for higher molecular weight fragments including SA1-III sequence (Congote et al, 2008). Other activities such as stimulation of proliferation and in vitro wound healing (Fumakia and Ho, 2016) do not appear to be conserved within the 409-418 sequence. As for the anti-inflammatory action, we have not found any effect of the peptide on IL-1b, IL-6, and TNF-a gene expression either at rest or in pro-inflammatory conditions (LPS stimulation).…”

Section: Discussionmentioning

confidence: 70%

Serpin A1 and the modulation of type I collagen turnover: Effect of the C‐terminal peptide 409–418 (SA1‐III) in human dermal fibroblasts

Cipriani

Pascarella

Errante

et al. 2018

Cell Biology International

View full text Add to dashboard Cite

The pharmacological modulation of collagen turnover is a strategy potentially useful in different skin conditions. The serine protease inhibitor Serpin A1 and portions of its C-terminal region have been investigated as collagen modulators. To clarify the mechanisms by which the C-terminal 409-418 peptide SA1-III increases extracellular type I collagen levels, to compare its activities range with that of the originator molecule Serpin A1, and to evaluate its efficacy in primary cultures from adult and aged human subjects. The different forms of type I collagen were analyzed by means of western blot in cell lysates and cell-conditioned media of primary human dermal fibroblasts obtained from subjects of different ages. Gelatin zymography was used to investigate the degrading enzymes. Cell viability and in vitro wound healing tests were used to evaluate cell proliferation. The SA1-III peptide increased extracellular collagen levels by reducing degradation, with no effect on cellular biosynthesis or cell proliferation mechanisms. A reduced level of MMP-2 and MMP-9 was also found in cell media upon peptide treatment. No peptide effect was detected on inflammatory mediators gene expression in resting and LPS-stimulated fibroblasts, or in the wound healing test. The SA1-III peptide is a good collagen modulator candidate, protecting collagen against degradation without detectable actions on biosynthesis, acting at reasonably low concentrations, and non-interfering with cell proliferation. It is effective in primary fibroblasts from young and aged subjects. These effects can prove useful in pathological and physiological skin conditions in which collagen degradation is excessive compared to the synthetic capacity.

show abstract

Section: Discussionmentioning

confidence: 70%

Serpin A1 and the modulation of type I collagen turnover: Effect of the C‐terminal peptide 409–418 (SA1‐III) in human dermal fibroblasts

Cipriani

Pascarella

Errante

et al. 2018

Cell Biology International

View full text Add to dashboard Cite

show abstract

“…Moreover, the co-encapsulation of LL37 and serpin A1 in solid lipid nanoparticles showed synergistic effect towards E. coli and S. aureus. for treatment of wound infections, although the mechanism of synergism was unknown [202].…”

Section: Nano Systems With Combination Drug Therapymentioning

confidence: 99%

Nanomedicine Fight against Antibacterial Resistance: An Overview of the Recent Pharmaceutical Innovations

et al. 2020

View full text Add to dashboard Cite

Based on the recent reports of World Health Organization, increased antibiotic resistance prevalence among bacteria represents the greatest challenge to human health. In addition, the poor solubility, stability, and side effects that lead to inefficiency of the current antibacterial therapy prompted the researchers to explore new innovative strategies to overcome such resilient microbes. Hence, novel antibiotic delivery systems are in high demand. Nanotechnology has attracted considerable interest due to their favored physicochemical properties, drug targeting efficiency, enhanced uptake, and biodistribution. The present review focuses on the recent applications of organic (liposomes, lipid-based nanoparticles, polymeric micelles, and polymeric nanoparticles), and inorganic (silver, silica, magnetic, zinc oxide (ZnO), cobalt, selenium, and cadmium) nanosystems in the domain of antibacterial delivery. We provide a concise description of the characteristics of each system that render it suitable as an antibacterial delivery agent. We also highlight the recent promising innovations used to overcome antibacterial resistance, including the use of lipid polymer nanoparticles, nonlamellar liquid crystalline nanoparticles, anti-microbial oligonucleotides, smart responsive materials, cationic peptides, and natural compounds. We further discuss the applications of antimicrobial photodynamic therapy, combination drug therapy, nano antibiotic strategy, and phage therapy, and their impact on evading antibacterial resistance. Finally, we report on the formulations that made their way towards clinical application.

show abstract

“…LL-37 and these agents acted synergistically in the treatment of full thickness excisional wounds, significantly promoting wound closure, reducing bacterial contamination and enhancing anti-inflammatory activity. These systems offered several advantages over therapies commonly used to treat chronic wound infections, which are often limited due to factors, such as the lack of controlled delivery and the depth of skin infections [249,250]. A number of LL-37 related peptides have also shown the potential for therapeutic development [243,251], such as OP-145, which was developed by OctoPlus, and when the peptide was included in cream formulations for nasal application, these preparations were found to be efficacious in the eradication of MRSA carriage [252].…”

Section: Potential Applications Of Ph Dependent Antimicrobial Peptmentioning

confidence: 99%

pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

et al. 2016

View full text Add to dashboard Cite

Antimicrobial peptides (AMPs) are potent antibiotics of the innate immune system that have been extensively investigated as a potential solution to the global problem of infectious diseases caused by pathogenic microbes. A group of AMPs that are increasingly being reported are those that utilise pH dependent antimicrobial mechanisms, and here we review research into this area. This review shows that these antimicrobial molecules are produced by a diverse spectrum of creatures, including vertebrates and invertebrates, and are primarily cationic, although a number of anionic examples are known. Some of these molecules exhibit high pH optima for their antimicrobial activity but in most cases, these AMPs show activity against microbes that present low pH optima, which reflects the acidic pH generally found at their sites of action, particularly the skin. The modes of action used by these molecules are based on a number of major structure/function relationships, which include metal ion binding, changes to net charge and conformational plasticity, and primarily involve the protonation of histidine, aspartic acid and glutamic acid residues at low pH. The pH dependent activity of pore forming antimicrobial proteins involves mechanisms that generally differ fundamentally to those used by pH dependent AMPs, which can be described by the carpet, toroidal pore and barrel-stave pore models of membrane interaction. A number of pH dependent AMPs and antimicrobial proteins have been developed for medical purposes and have successfully completed clinical trials, including kappacins, LL-37, histatins and lactoferrin, along with a number of their derivatives. Major examples of the therapeutic application of these antimicrobial molecules include wound healing as well as the treatment of multiple cancers and infections due to viruses, bacteria and fungi. In general, these applications involve topical administration, such as the use of mouth washes, cream formulations and hydrogel delivery systems. Nonetheless, many pH dependent AMPs and antimicrobial proteins have yet to be fully characterized and these molecules, as a whole, represent an untapped source of novel biologically active agents that could aid fulfillment of the urgent need for alternatives to conventional antibiotics, helping to avert a return to the pre-antibiotic era.

show abstract

Nanoparticles Encapsulated with LL37 and Serpin A1 Promotes Wound Healing and Synergistically Enhances Antibacterial Activity

Cited by 106 publications

References 74 publications

Serpin A1 and the modulation of type I collagen turnover: Effect of the C‐terminal peptide 409–418 (SA1‐III) in human dermal fibroblasts

Serpin A1 and the modulation of type I collagen turnover: Effect of the C‐terminal peptide 409–418 (SA1‐III) in human dermal fibroblasts

Nanomedicine Fight against Antibacterial Resistance: An Overview of the Recent Pharmaceutical Innovations

pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

Contact Info

Product

Resources

About