Lipid Nanocarriers Impede Side Effects of Delivered Antimicrobial Peptide

Berest, V. P.; Sotnikov, Anatolii; Sichevska, Larysa

doi:10.1109/ukrcon53503.2021.9575721

Cited by 3 publications

(2 citation statements)

References 9 publications

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“…Але загальної картини взаємодії граміцидину S з клітинами не має, завдяки тому що його вплив на різні типи клітин не є однаковим [3,11,28]. З огляду на вивчення можливості системного застосування аналогів або інкапсульованих наноносіями форм антимікробних пептидів [29] цікавим було вивчення впливу GS на клітин сполучної тканини на додачу до робіт з вивчення впливу цього циклічного пептиду на клітини крові [3,4,28,30]. Таблиця 5.…”

Section: результати та обговоренняunclassified

The antimicrobial peptide gramicidin S alters proliferation and inhibits adhesion of L929 cell line fibroblasts

Alabedalkarim,

Berest,

Moiseieva

et al. 2023

Biophysical Bulletin

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Background: Natural antimicrobial peptides are used in the fight against pathogens resistant to existing synthetic antibiotics. The non-specific mechanism of cytostatic action of antimicrobial peptides, in particular gramicidin S, against bacteria is also effective for damaging the cells of neoplasms. The existence of such a property in a registered antibiotic will indicate its antineoplastic potential and can be used to expand the spectrum of its therapeutic application. Aim of work is to clarify the possible antitumor effect of the antimicrobial peptide gramicidin S. Materials and Methods: Using the methods of confocal laser microscopy and light microscopy, the morphological and functional features of connective tissue cells under the influence of gramicidin S in the concentration range 0.5–50 μg/ml were studied using L929 fibroblasts cell culture. The cell area, nucleus area, and nucleus-to-cytoplasm ratio were determined. To study the migratory and proliferative activity of cells in vitro, the “scratch assay” was used, the confluency of the monolayer of cells was evaluated, morphometric studies were performed, and the relative area of the scratch was measured after 24, 48, and 72 hours. Results: The lytic effect of gramicidin S in a concentration of 50 μg/ml on L929 cells was established, in concentrations of 0.5 μg/ml and 5.0 μg/ml, the antibiotic increases the synthetic activity of cells and stimulates the proliferation of fibroblasts in a monolayer. Cell anisomorphism is more pronounced in the presence of 5.0 μg/ml gramicidin S added to the culturing medium during monolayer formation, while a one-third of the cells in the sample form a population that is morphologically different from other cells in the culture. The addition of gramicidin S at non-lytic concentrations of 0.5 and 5.0 μg/ml to unattached fibroblasts reliably inhibits monolayer formation. Under the influence of 5.0 μg/ml gramicidin S, the rate of monolayer formation is low, even despite the significant content of cells with a high nuclear-cytoplasmic ratio. The kinetics of filling the cell monolayer defect using the “scratch assay” shows that GS in concentrations of 0.5 and 5.0 μg/ml can control the migratory and proliferative properties of L929 cells. Conclusions: The effect of gramicidin S on the morphometric parameters of cells depends on the concentration of the peptide and the cell status in the culture. GS corrupts the adhesive properties of L929 fibroblasts in monolayer cell culture and the rate of cell monolayer formation. Cells at the stage of attachment and monolayer formation were most sensitive to non-lytic concentrations of GS. Inhibition of the adhesive properties of connective tissue cells by gramicidin S is a new non-canonical effect of a known antimicrobial drug, which may indicate the possibility of using gramicidin S as an anti-neoplasm agent.

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Section: результати та обговоренняunclassified

The antimicrobial peptide gramicidin S alters proliferation and inhibits adhesion of L929 cell line fibroblasts

Alabedalkarim,

Berest,

Moiseieva

et al. 2023

Biophysical Bulletin

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“…Це додаткові до гемолізу еритроцитів несприятливі фактори впливу «прямого» застосування GS через системний кровообіг. Можливість корегування гемолітичної дії GS шляхом застосування комплексів антибіотику із наноносіями та модифікації структури пептиду показано в роботах [20,21,2]. Перевагою першого підходу є використання нової лікарської форми зареєстрованого фармпрепарату, позаяк переваги хімічно модифікованих аналогів, які спостерігалися in vitro, мають бути підтверджені та пройти тривалу процедуру погодження та реєстрації нового лікарського засобу.…”

Section: результати та обговоренняunclassified

Changes in electrophysical characteristics of red blood cells induced by gramicidin S

Ovsyannikova

Kovalenko

Berest

et al. 2021

Biophysical Bulletin

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Background. The use of antimicrobial peptides is one of the possible ways to overcome the threatening rapid growth of resistance of microorganisms to traditional antibiotics. Of the particular role in this context is gramicidin S (GS), which is used for topical medical applications for over 70 years. An acute hemolytic side effect of GS on human cells prevents its systemic use. Understanding the molecular mechanisms of interaction of GS with biological membranes will enhance its bactericidal effect on the one hand, and reduce the negative side effects on human cells and thus expand the range of antibacterial peptides to combat infectious diseases caused by resistant microorganisms. Objectives. Study of the effect of different doses of the antimicrobial oligopeptide antibiotic GS on the morphological and electrophysical characteristics of human erythrocytes during in vitro incubation. Materials and methods. Morphological changes of erythrocytes of healthy donors after preliminary incubation with GS at concentrations 5–40 μg/ml were studied by flow cytometry using resistance pulse spectroscopy. Single-cell volume, erythrocyte volume distribution in the population was measured, and the electrical breakdown potential of the human erythrocyte plasma membrane was determined. Results. Incubation of human erythrocytes with sub-lytic concentrations of GS is accompanied by a redistribution of erythrocytes in this population by volume with an increased number of smaller erythrocytes with less resistance of the membrane to electrical breakdown. However, increasing the concentration of GS to 40 μg/ml leads to an increase in the proportion of cells of increased volume with increased resistance to electrical breakdown of the membrane. Possible mechanisms of morphological changes of erythrocytes under the action of GS are discussed. Conclusions. Incubation of erythrocytes with GS at concentrations 5–40 μg/ml is accompanied by a redistribution of cells by volume and changes in the resistance of their plasma membrane to electrical breakdown due to destabilizing membrane-tropic action of the peptide, microsimulation, or cytoskeleton rearrangement.

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Modifying Membranotropic Action of Antimicrobial Peptide Gramicidin S by Star-like Polyacrylamide and Lipid Composition of Nanocontainers

Vashchenko,

Berest,

Sviechnikova

et al. 2024

IJMS

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Gramicidin S (GS), one of the first discovered antimicrobial peptides, still shows strong antibiotic activity after decades of clinical use, with no evidence of resistance. The relatively high hemolytic activity and narrow therapeutic window of GS limit its use in topical applications. Encapsulation and targeted delivery may be the way to develop the internal administration of this drug. The lipid composition of membranes and non-covalent interactions affect GS’s affinity for and partitioning into lipid bilayers as monomers or oligomers, which are crucial for GS activity. Using both differential scanning calorimetry (DSC) and FTIR methods, the impact of GS on dipalmitoylphosphatidylcholine (DPPC) membranes was tested. Additionally, the combined effect of GS and cholesterol on membrane characteristics was observed; while dipalmitoylphosphatydylglycerol (DPPG) and cerebrosides did not affect GS binding to DPPC membranes, cholesterol significantly altered the membrane, with 30% mol concentration being most effective in enhancing GS binding. The effect of star-like dextran-polyacrylamide D-g-PAA(PE) on GS binding to the membrane was tested, revealing that it interacted with GS in the membrane and significantly increased the proportion of GS oligomers. Instead, calcium ions affected GS binding to the membrane differently, with independent binding of calcium and GS and no interaction between them. This study shows how GS interactions with lipid membranes can be effectively modulated, potentially leading to new formulations for internal GS administration. Modified liposomes or polymer nanocarriers for targeted GS delivery could be used to treat protein misfolding disorders and inflammatory conditions associated with free-radical processes in cell membranes.

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Lipid Nanocarriers Impede Side Effects of Delivered Antimicrobial Peptide

Cited by 3 publications

References 9 publications

The antimicrobial peptide gramicidin S alters proliferation and inhibits adhesion of L929 cell line fibroblasts

The antimicrobial peptide gramicidin S alters proliferation and inhibits adhesion of L929 cell line fibroblasts

Changes in electrophysical characteristics of red blood cells induced by gramicidin S

Modifying Membranotropic Action of Antimicrobial Peptide Gramicidin S by Star-like Polyacrylamide and Lipid Composition of Nanocontainers

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