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Cationic Nanoparticles: Options to Replace Antibiotics against Multi-Drugs Resistant Pathogens
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Cationic Nanoparticles: Options to Replace Antibiotics against Multi-Drugs Resistant Pathogens

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Nanoscience".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 9152

Special Issue Editors

Prof. Dr. Silvana Alfei

E-Mail Website
Guest Editor
Department of Pharmacy, University of Genoa, Viale Cembrano, 16148 Genoa, Italy
Interests: nanomaterials; dendrimers; macromolecules; hydrogels for biomedical and environmental applications; resins; polymeric drug delivery systems; organic synthesis; antibacterial and/or antitumor cationic macromolecules; solubilizing agents
Special Issues, Collections and Topics in MDPI journals
Dr. Anna Maria Schito

E-Mail Website
Guest Editor
Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Viale Benedetto XV, 6, I-16132 Genova, Italy
Interests: new antimicrobials; natural agents as antimicrobials; natural agents as antibiofilm agents; Gram negative and Gram positive multiresistant pathogens; modulation of virulence traits
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Multidrug-resistant pathogens, often responsible for severe and incurable infections, are a worldwide concern urgently requiring efforts to find new treatment options. Both Gram-negative and Gram-positive bacilli are emerging as clinically relevant superbugs, often sensitive only to certain natural cationic antimicrobial peptides (AMPs) capable of lethally interacting with bacterial membranes and killing them rapidly, regardless of their drug resistance. More stable and low-cost cationic macromolecules, mimicking AMPs, are continuously synthesized and tested on various pathogenic bacterial species, with the aim of reducing the incidence of fatal infections in both the general population and fragile individuals. Cationic macromolecules can electrostatically interact with the bacterial surface and cause harmful and irreversible changes to the integrity of the membrane, thus leading to the loss of bacterial cytoplasmic content and cell death. However, this area is still largely unexplored, and further collective efforts are needed to contain the worrying decline in the number of effective antibiotics, the rising healthcare costs due to increasingly frequent hospitalizations, and to investigate the mechanisms of action of cationic macromolecules.

This Special Issue aims to include articles and reviews on cationic antimicrobial materials and structural strategies to improve their antibacterial activity, selectivity, carrying capacity, as well as studies investigating molecular mechanisms of action. Furthermore, studies of formulations of the developed agents, characterized by antibacterial activity and low cytotoxicity toward mammalian cells, will be welcome.


Dr. Silvana Alfei
Dr. Anna Maria Schito
Guest Editors

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Keywords

  • Multi-drug resistant Gram-negative and Gram-positive pathogens
  • Clinically relevant superbugs
  • Severe and almost untreatable infections
  • Immunocompromised individuals
  • Synthetic antimicrobial cationic macromolecules
  • Synthetic cationic dendrimers, polymers, and copolymers
  • Polymerizing strategies
  • Natural and synthetic polypeptides
  • Amino-acid modified macromolecules
  • Electrostatic interactions and membrane permeabilization
  • Membrane disruptors
  • Drug delivery systems

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Published Papers (3 papers)

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Research

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26 pages, 7883 KiB  
Article
Hydrogel Formulations of Antibacterial Pyrazoles Using a Synthesized Polystyrene-Based Cationic Resin as a Gelling Agent
by Silvana Alfei, Guendalina Zuccari, Eleonora Russo, Carla Villa and Chiara Brullo
Int. J. Mol. Sci. 2023, 24(2), 1109; https://doi.org/10.3390/ijms24021109 - 6 Jan 2023
Cited by 5 | Viewed by 1751
Abstract
Here, to develop new topical antibacterial formulations to treat staphylococcal infections, two pyrazoles (3c and 4b) previously reported as antibacterial agents, especially against staphylococci, were formulated as hydrogels (R1-HG-3c and R1HG-4b) using a cationic polystyrene-based resin (R1) and here synthetized and [...] Read more.
Here, to develop new topical antibacterial formulations to treat staphylococcal infections, two pyrazoles (3c and 4b) previously reported as antibacterial agents, especially against staphylococci, were formulated as hydrogels (R1-HG-3c and R1HG-4b) using a cationic polystyrene-based resin (R1) and here synthetized and characterized as gelling agents. Thanks to the high hydrophilicity, high-level porosity, and excellent swelling capabilities of R1, R1HG-3c and R1HG-4b were achieved with an equilibrium degree of swelling (EDS) of 765% (R1HG-3c) and 675% (R1HG-4b) and equilibrium water content (EWC) of 88% and 87%, respectively. The chemical structure of soaked and dried gels was investigated by PCA-assisted attenuated total reflectance (ATR) Fourier transform infrared (FTIR) spectroscopy, while their morphology was investigated by optical microscopy. Weight loss studies were carried out with R1HG-3c and R1HG-4b to investigate their water release profiles and the related kinetics, while their stability was evaluated over time both by monitoring their inversion properties to detect possible impairments of the 3D network and by PCA-assisted ATR-FTIR spectroscopy to detect possible structural changes. The flow and dynamic rheological characterization of the gels was assessed by determining their viscosity vs. shear rate, applying the Cross rheological equation to achieve the curves of shear stress vs. shear rate, and carrying out amplitude and frequency sweep experiments. Finally, their content in NH3+ groups was determined by potentiometric titrations. Due to their favorable physicochemical characteristic and the antibacterial effects of 3c and 4b possibly improved by the cationic R1, the pyrazole-enriched gels reported here could represent new weapons to treat severe skin and wound infections sustained by MDR bacteria of staphylococcal species. Full article
(This article belongs to the Special Issue Cationic Nanoparticles: Options to Replace Antibiotics against Multi-Drugs Resistant Pathogens)
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23 pages, 4263 KiB  
Article
Bactericidal Activity of a Self-Biodegradable Lysine-Containing Dendrimer against Clinical Isolates of Acinetobacter Genus
by Silvana Alfei, Debora Caviglia, Gabriella Piatti, Guendalina Zuccari and Anna Maria Schito
Int. J. Mol. Sci. 2021, 22(14), 7274; https://doi.org/10.3390/ijms22147274 - 6 Jul 2021
Cited by 10 | Viewed by 2250
Abstract
The genus Acinetobacter consists of Gram-negative obligate aerobic pathogens, including clinically relevant species, such as A. baumannii, which frequently cause hospital infections, affecting debilitated patients. The growing resistance to antimicrobial therapies shown by A. baumannii is reaching unacceptable levels in clinical practice, [...] Read more.
The genus Acinetobacter consists of Gram-negative obligate aerobic pathogens, including clinically relevant species, such as A. baumannii, which frequently cause hospital infections, affecting debilitated patients. The growing resistance to antimicrobial therapies shown by A. baumannii is reaching unacceptable levels in clinical practice, and there is growing concern that the serious conditions it causes may soon become incurable. New therapeutic possibilities are, therefore, urgently needed to circumvent this important problem. Synthetic cationic macromolecules, such as cationic antimicrobial peptides (AMPs), which act as membrane disrupters, could find application in these conditions. A lysine-modified cationic polyester-based dendrimer (G5-PDK), capable of electrostatically interacting with bacterial surfaces as AMPs do, has been synthesized and characterized here. Given its chemical structure, similar to that of a fifth-generation lysine containing dendrimer (G5K) with a different core, and previously found inactive against Gram-positive bacterial species and Enterobacteriaceae, the new G5-PDK was also ineffective on the species mentioned above. In contrast, it showed minimum inhibitory concentration values (MICs) lower than reported for several AMPs and other synthetic cationic compounds on Acinetobacter genus (3.2–12.7 µM). Time-kill experiments on A. baumannii, A. pittii, and A. ursingii ascertained the rapid bactericidal effects of G5-PDK, while subsequent bacterial regrowth supported its self-biodegradability. Full article
(This article belongs to the Special Issue Cationic Nanoparticles: Options to Replace Antibiotics against Multi-Drugs Resistant Pathogens)
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Review

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18 pages, 1918 KiB  
Review
Antimicrobial Peptides and Cationic Nanoparticles: A Broad-Spectrum Weapon to Fight Multi-Drug Resistance Not Only in Bacteria
by Giulia E. Valenti, Silvana Alfei, Debora Caviglia, Cinzia Domenicotti and Barbara Marengo
Int. J. Mol. Sci. 2022, 23(11), 6108; https://doi.org/10.3390/ijms23116108 - 29 May 2022
Cited by 24 | Viewed by 3766
Abstract
In the last few years, antibiotic resistance and, analogously, anticancer drug resistance have increased considerably, becoming one of the main public health problems. For this reason, it is crucial to find therapeutic strategies able to counteract the onset of multi-drug resistance (MDR). In [...] Read more.
In the last few years, antibiotic resistance and, analogously, anticancer drug resistance have increased considerably, becoming one of the main public health problems. For this reason, it is crucial to find therapeutic strategies able to counteract the onset of multi-drug resistance (MDR). In this review, a critical overview of the innovative tools available today to fight MDR is reported. In this direction, the use of membrane-disruptive peptides/peptidomimetics (MDPs), such as antimicrobial peptides (AMPs), has received particular attention, due to their high selectivity and to their limited side effects. Moreover, similarities between bacteria and cancer cells are herein reported and the hypothesis of the possible use of AMPs also in anticancer therapies is discussed. However, it is important to take into account the limitations that could negatively impact clinical application and, in particular, the need for an efficient delivery system. In this regard, the use of nanoparticles (NPs) is proposed as a potential strategy to improve therapy; moreover, among polymeric NPs, cationic ones are emerging as promising tools able to fight the onset of MDR both in bacteria and in cancer cells. Full article
(This article belongs to the Special Issue Cationic Nanoparticles: Options to Replace Antibiotics against Multi-Drugs Resistant Pathogens)
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