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Pharmaceutics
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New Strategies for Combating Antibiotic Resistance Based on Organic and...
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New Strategies for Combating Antibiotic Resistance Based on Organic and Inorganic Nanosystems

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: closed (20 February 2023) | Viewed by 12099

Special Issue Editors

Dr. Elia M. Grueso

E-Mail Website
Guest Editor
Department of Physical Chemistry, Faculty of Chemistry, University of Seville, 41012 Seville, Spain
Interests: drug delivery; drug carriers; nanomedicine; nanoparticles; gemini surfactants; biopolymers
Special Issues, Collections and Topics in MDPI journals
Dr. Rosa María Giráldez-Pérez

E-Mail Website
Guest Editor
Department of Cellular Biology, Physiology and Immunology, Faculty of Science, University of Córdoba, 14014 Cordoba, Spain
Interests: biotechnology; biochemistry; neurodegeneration and related iseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Antibiotic resistance prevalence among bacteria constitutes a major problem for human health which requires the investigation of new, more effective drugs. Various mechanisms, such as modification of the therapeutic target or inactivation by enzymes, can cause the survival of the microorganism and even make it multiresistant. To date, this problem has been solved with the design of new drugs that are increasingly complex at the structural level. However, bacteria continue developing new resistance due to the excessive and repeated drug doses required to control infection, among other reasons. Furthermore, there are additional aspects to overcome in free drug administration related to poor solubility in water, low stability, and side effects, which require a search for new innovative strategies. Among them, organic and inorganic nanosystems stand out in the domain of antibacterial delivery agents versus conventional antibiotic therapies. This Special Issue invites international researchers in the area of the design and preparation of new nanosystems for combating antibiotic resistance. Physicochemical properties of nanosystems such as particle size, surface charge, high surface area to volume ratio, low toxicity, solubility, and excellent biocompatibility and stability can help to control vital processes such as intracellular uptake and biodistribution, improving drug clinical efficiency.

Dr. Elia M. Grueso
Dr. Rosa María Giráldez-Pérez
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antibiotic resistance
  • drug delivery
  • drug carriers
  • nanoparticles
  • nanomedicine
  • biomolecules
  • conformational changes

Published Papers (5 papers)

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Research

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24 pages, 4253 KiB  
Article
Tackling Antibiotic Resistance: Influence of Aliphatic Branches on Broad-Spectrum Antibacterial Polytriazoles against ESKAPE Group Pathogens
by Cristian Rangel-Núñez, Inmaculada Molina-Pinilla, Cristina Ramírez-Trujillo, Adrián Suárez-Cruz, Samuel Bernal Martínez and Manuel Bueno-Martínez
Pharmaceutics 2022, 14(11), 2518; https://doi.org/10.3390/pharmaceutics14112518 - 19 Nov 2022
Cited by 1 | Viewed by 1277
Abstract
One of the most important threats to public health is the appearance of multidrug-resistant pathogenic bacteria, since they are the cause of a high number of deaths worldwide. Consequently, the preparation of new effective antibacterial agents that do not generate antimicrobial resistance is [...] Read more.
One of the most important threats to public health is the appearance of multidrug-resistant pathogenic bacteria, since they are the cause of a high number of deaths worldwide. Consequently, the preparation of new effective antibacterial agents that do not generate antimicrobial resistance is urgently required. We report on the synthesis of new linear cationic antibacterial polytriazoles that could be a potential source of new antibacterial compounds. These polymers were prepared by thermal- or copper-catalyzed click reactions of azide and alkyne functions. The antibacterial activity of these materials can be modulated by varying the size or nature of their side chains, as this alters the hydrophilic/hydrophobic balance. Antibacterial activity was tested against pathogens of the ESKAPE group. The P3TD polymer, which has butylated side chains, was found to have the highest bactericidal activity. The toxicity of selected polytriazoles was investigated using human red blood cells and a human gingival fibroblast cell line. The propensity of prepared polytriazoles to induce resistance in certain bacteria was studied. Some of them were found to not produce resistance in methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa. The interaction of these polytriazoles with the Escherichia coli membrane produces both depolarization and disruption of the membrane. Full article
(This article belongs to the Special Issue New Strategies for Combating Antibiotic Resistance Based on Organic and Inorganic Nanosystems)
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40 pages, 4001 KiB  
Article
Achyranthes aspera Extracts as Adjuvants for the Redressal of Antibiotic Resistance
by Hamna Ahmad, Umar Farooq Gohar, Hamid Mukhtar, Muhammad Zia-UI-Haq, Romina Alina Marc, Marius Irimie, Luigi Geo Marceanu and Claudia Mihaela Gavris
Pharmaceutics 2022, 14(10), 2219; https://doi.org/10.3390/pharmaceutics14102219 - 18 Oct 2022
Cited by 1 | Viewed by 2003
Abstract
Achyranthes aspera seeds and leaves are believed to reverse antibiotic resistance and increase the efficacy of current drugs. Achyranthes aspera seeds and leaves contain many secondary metabolites needed for the redressal of antibiotic resistance. In the present study, seven different antibiotics were used [...] Read more.
Achyranthes aspera seeds and leaves are believed to reverse antibiotic resistance and increase the efficacy of current drugs. Achyranthes aspera seeds and leaves contain many secondary metabolites needed for the redressal of antibiotic resistance. In the present study, seven different antibiotics were used against five different strains of bacteria such as Methicillin-resistant Staphylococcus aureus, Enterococcus faecalis, Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. For Methicillin-resistant Staphylococcus aureus Cefoxitin, Penicillin, and Co-trimoxazole were resistant out of seven antibiotics. The zone of inhibition for all these three antibiotics goes from the resistant to the sensitive range after the combination with plant extracts. For Enterococcus faecalis, Ciprofloxacin, Levofloxacin, Penicillin, Amoxicillin, Imipenem, and Vancomycin were resistant after treatment with the plant extracts, and the Ciprofloxacin, Levofloxacin, Imipenem, and Vancomycin zones of inhibition were from the resistant to the sensitive range. An increase in zone sizes was observed for Penicillin, but it remained resistant while no zone of inhibition was observed for Amoxicillin. For Acinetobacter baumannii, Ciprofloxacin, Levofloxacin, Ceftriaxone, Ceftazidime, and Imipenem were resistant. After a combination of these antibiotics with plant extracts, a change in zone sizes was observed for Levofloxacin and Ceftriaxone, but it was not considerable as it remained in the resistance and intermediate ranges. No zones of inhibition were observed for Ciprofloxacin, Ceftazidime, or Imipenem. For Klebsiella pneumoniae, all the antibiotics were resistant. An increase in zone sizes was observed after a combination with plant extracts for Ceftazidime and Imipenem in Klebsiella pneumoniae, but it remained in the resistance category. No zone of inhibition was observed for Pseudomonas aeruginosa before or after using plant extracts against any antibiotic. This study suggests that the Achyranthes aspera seed and leaf extracts can reverse antibiotic resistance without any side effects on the human body, and that they can reverse antibiotic resistance naturally. Full article
(This article belongs to the Special Issue New Strategies for Combating Antibiotic Resistance Based on Organic and Inorganic Nanosystems)
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30 pages, 5874 KiB  
Article
Use of Nanoparticles to Prevent Resistance to Antibiotics—Synthesis and Characterization of Gold Nanosystems Based on Tetracycline
by Rosa M. Giráldez-Pérez, Elia M. Grueso, Raquel Jiménez-Aguayo, Alfonso Carbonero, Marina González-Bravo, Edyta Kuliszewska and Rafael Prado-Gotor
Pharmaceutics 2022, 14(9), 1941; https://doi.org/10.3390/pharmaceutics14091941 - 14 Sep 2022
Cited by 2 | Viewed by 1942
Abstract
Antimicrobial resistance (AMR) is a serious public health problem worldwide which, according to the World Health Organization (WHO), requires research into new and more effective drugs. In this work, both gold nanoparticles covered with 16-3-16 cationic gemini surfactant (Au@16-3-16) and DNA/tetracycline (DNA/TC) intercalated [...] Read more.
Antimicrobial resistance (AMR) is a serious public health problem worldwide which, according to the World Health Organization (WHO), requires research into new and more effective drugs. In this work, both gold nanoparticles covered with 16-3-16 cationic gemini surfactant (Au@16-3-16) and DNA/tetracycline (DNA/TC) intercalated complexes were prepared to effectively transport tetracycline (TC). Synthesis of the Au@16-3-16 precursor was carried out by using trihydrated gold, adding sodium borohydride as a reducing agent and the gemini surfactant 16-3-16 as stabilizing agent. Circular dichroism and atomic force microscopy techniques were then used to ascertain the optimal R range of the relationship between the concentrations of Au@16-3-16 and the DNA/TC complex (R = CAu@16-3-16/CDNA) that allow the obtainment of stable and compact nanosystems, these characteristics being fundamental for their use as antibiotic transporters. Stability studies over time were carried out for distinct selected Au@16-3-16 and Au@16-3-16/DNA-TC nanoformulations using the ultraviolet–visible spectrophotometry technique, checking their stability for at least one month. In addition, in order to know the charge and size distribution of the nanocomplexes, DLS and zeta potential measurements were performed in the solution. The results showed that the characterized nanosystems were highly charged, stable and of a reduced size (<100 nm) that allows them to cross bacterial membranes effectively (>1 μm). Once the different physicochemical characteristics of the gold nanosystems were measured, Au@16-3-16 and Au@16-3-16/DNA-TC were tested on Escherichia coli and Staphylococcus aureus to study their antibacterial properties and internalization capacity in microbes. Differences in the interaction of the precursors and the compacted nanosystems generated were observed in Gram-positive and Gram-negative bacteria, possibly due to membrane damage or electrostatic interaction with internalization by endocytosis. In the internalization experiments, depending on the treatment application time, the greatest bacterial destruction was observed for all nanoformulations explored at 18 h of incubation. Importantly, the results obtained demonstrate that both new nanosystems based on TC and Au@16-3-16 precursors have optimal antimicrobial properties and would be beneficial for use in patients, avoiding possible side effects. Full article
(This article belongs to the Special Issue New Strategies for Combating Antibiotic Resistance Based on Organic and Inorganic Nanosystems)
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Review

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31 pages, 5302 KiB  
Review
Functionalized Self-Assembled Monolayers: Versatile Strategies to Combat Bacterial Biofilm Formation
by Pamela M. Lundin, Briana L. Fiser, Meghan S. Blackledge, Hannah L. Pickett and Abigail L. Copeland
Pharmaceutics 2022, 14(8), 1613; https://doi.org/10.3390/pharmaceutics14081613 - 02 Aug 2022
Cited by 7 | Viewed by 2391
Abstract
Bacterial infections due to biofilms account for up to 80% of bacterial infections in humans. With the increased use of antibiotic treatments, indwelling medical devices, disinfectants, and longer hospital stays, antibiotic resistant infections are sharply increasing. Annual deaths are predicted to outpace cancer [...] Read more.
Bacterial infections due to biofilms account for up to 80% of bacterial infections in humans. With the increased use of antibiotic treatments, indwelling medical devices, disinfectants, and longer hospital stays, antibiotic resistant infections are sharply increasing. Annual deaths are predicted to outpace cancer and diabetes combined by 2050. In the past two decades, both chemical and physical strategies have arisen to combat biofilm formation on surfaces. One such promising chemical strategy is the formation of a self-assembled monolayer (SAM), due to its small layer thickness, strong covalent bonds, typically facile synthesis, and versatility. With the goal of combating biofilm formation, the SAM could be used to tether an antibacterial agent such as a small-molecule antibiotic, nanoparticle, peptide, or polymer to the surface, and limit the agent’s release into its environment. This review focuses on the use of SAMs to inhibit biofilm formation, both on their own and by covalent grafting of a biocidal agent, with the potential to be used in indwelling medical devices. We conclude with our perspectives on ongoing challenges and future directions for this field. Full article
(This article belongs to the Special Issue New Strategies for Combating Antibiotic Resistance Based on Organic and Inorganic Nanosystems)
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17 pages, 3937 KiB  
Review
Nanomaterials Aiming to Tackle Antibiotic-Resistant Bacteria
by Muhammad Usman Munir and Muhammad Masood Ahmad
Pharmaceutics 2022, 14(3), 582; https://doi.org/10.3390/pharmaceutics14030582 - 07 Mar 2022
Cited by 28 | Viewed by 3507
Abstract
The global health of humans is seriously affected by the dramatic increases in the resistance patterns of antimicrobials against virulent bacteria. From the statements released by the Centers for Disease Control and Prevention about the world entering a post-antibiotic era, and forecasts about [...] Read more.
The global health of humans is seriously affected by the dramatic increases in the resistance patterns of antimicrobials against virulent bacteria. From the statements released by the Centers for Disease Control and Prevention about the world entering a post-antibiotic era, and forecasts about human mortality due to bacterial infection being increased compared to cancer, the current body of literature indicates that emerging tools such as nanoparticles can be used against lethal infections caused by bacteria. Furthermore, a different concept of nanomaterial-based methods can cope with the hindrance faced by common antimicrobials, such as resistance to antibiotics. The current review focuses on different approaches to inhibiting bacterial infection using nanoparticles and aiding in the fabrication of antimicrobial nanotherapeutics by emphasizing the functionality of nanomaterial surface design and fabrication for antimicrobial cargo. Full article
(This article belongs to the Special Issue New Strategies for Combating Antibiotic Resistance Based on Organic and Inorganic Nanosystems)
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