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Polymers
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Positively Charged Antimicrobial Dendrimers
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Positively Charged Antimicrobial Dendrimers

A special issue of Polymers (ISSN 2073-4360). This special issue belongs to the section "Polymer Applications".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 7826

Special Issue Editors

Prof. Dr. Silvana Alfei

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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

The rapid increase of antimicrobial resistance urgently requires new curative options. Inspired by natural cationic antimicrobial peptides, cationic molecules able to inhibit or kill bacteria, acting principally as external membrane disruptors, were synthetized.

Cationic antimicrobial dendrimers, compared to small drug molecules or traditional polymers, own improved long-term activity, selectivity, stability, and better capability to load traditional antibiotics, working in synergy and allowing reduced dosage.

In this contest, differently structured cationic dendrimers were industrialized, but the developing of polyester-based ones, in our opinion very attractive, because highly biodegradable, is still in its infancy. Additionally, their mechanism of action at molecular level, as well as the relationships structure/activity need more investigations.

This Special Issue wants to present the latest solutions in the field of antimicrobial cationic dendrimers, the structural strategies to improve their activity, selectivity and drug loading capacity and aim at providing information concerning their mechanisms of action.

Keywords

  • Gram-positive and Gram-negative bacteria
  • antibiotic-resistant nosocomial pathogens
  • novel bactericidal agents
  • polycationic dendrimers
  • polyester-based dendrimers
  • amino-acid modified dendrimers
  • membrane disruptors
  • minimum inhibitory concentration (MIC)

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Published Papers (2 papers)

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16 pages, 1617 KiB  
Article
Synthesis and Antibacterial Activity of Cationic Amino Acid-Conjugated Dendrimers Loaded with a Mixture of Two Triterpenoid Acids
by Anna Maria Schito, Gian Carlo Schito and Silvana Alfei
Polymers 2021, 13(4), 521; https://doi.org/10.3390/polym13040521 - 9 Feb 2021
Cited by 26 | Viewed by 3034
Abstract
To counteract the growing bacterial resistance, we previously reported the remarkable antimicrobial activity of amino acid-conjugated cationic dendrimers (CDs) against several Gram-negative species, establishing that the cationic lysine was essential for their potency. In this paper, CDs conjugated with lysine and arginine and [...] Read more.
To counteract the growing bacterial resistance, we previously reported the remarkable antimicrobial activity of amino acid-conjugated cationic dendrimers (CDs) against several Gram-negative species, establishing that the cationic lysine was essential for their potency. In this paper, CDs conjugated with lysine and arginine and encapsulating ursolic and oleanolic acids (UOACDs) were assumed to be excellent candidates for developing new antibacterial agents, possibly active against Gram-positive species. Indeed, both the guanidine group of arginine and the two triterpenoid acids are items known for directing antibacterial effects, particularly against Gram-positive bacteria. The cationic dendrimers were obtained by peripheral conjugation with the selected amino acids and by entrapping a physical mixture of the commercial triterpenoid acids. The cationic compounds were characterized and successfully tested against 15 Gram-positive isolates. Interesting minimum inhibitory concentration (MIC) values were obtained for all the dendrimer-drug agents, establishing that the antibacterial activity observed for the UOACDs strongly depended on the density and on the type of the cationic groups of the cationic amino acid-conjugated dendrimers and not on the presence and the release of UOA. Particularly, lysine was critical for potency, while arginine was critical for redirecting activity against Gram-positive species. Especially, a high cationic character, associated with a balanced content of lysine/arginine, produced a remarkable antimicrobial effect (MIC = 0.5–8.7 µM). Full article
(This article belongs to the Special Issue Positively Charged Antimicrobial Dendrimers)
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13 pages, 1659 KiB  
Article
Antibacterial Activity of Non-Cytotoxic, Amino Acid-Modified Polycationic Dendrimers against Pseudomonas aeruginosa and Other Non-Fermenting Gram-Negative Bacteria
by Anna Maria Schito and Silvana Alfei
Polymers 2020, 12(8), 1818; https://doi.org/10.3390/polym12081818 - 13 Aug 2020
Cited by 33 | Viewed by 3218
Abstract
Due to the rapid increase of antimicrobial resistance with ensuring therapeutic failures, the purpose of this study was to identify novel synthetic molecules as alternatives to conventional available, but presently ineffective antibiotics. Variously structured cationic dendrimers previously reported have provided promising outcomes. However, [...] Read more.
Due to the rapid increase of antimicrobial resistance with ensuring therapeutic failures, the purpose of this study was to identify novel synthetic molecules as alternatives to conventional available, but presently ineffective antibiotics. Variously structured cationic dendrimers previously reported have provided promising outcomes. However, the problem of their cytotoxicity towards eukaryotic cells has not been completely overcome. We have now investigated the antibacterial activities of three not cytotoxic cationic dendrimers (G5Ds: G5H, G5K, and G5HK) against several multidrug-resistant (MDR) clinical strains. All G5Ds displayed remarkable activity against MDR non-fermenting Gram-negative species such as P. aeruginosa, S. maltophilia, and A. baumannii (MICs = 0.5–33.2 µM). In particular, very low MIC values (0.5–2.1 µM) were observed for G5K, which proved to be more active than the potent colistin (2.1 versus 3.19 µM) against P. aeruginosa. Concerning its mechanism of action, in time-killing and turbidimetric studies, G5K displayed a rapid non-lytic bactericidal activity. Considering the absence of cytotoxicity of these new compounds and their potency, comparable or even higher than that provided by the dendrimers previously reported, G5Ds may be proposed as promising novel antibacterial agents capable of overcoming the alarming resistance rates of several nosocomial non-fermenting Gram-negative pathogens. Full article
(This article belongs to the Special Issue Positively Charged Antimicrobial Dendrimers)
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