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Pharmaceutics
Special Issues
Application of Nanoparticles and Dendrimers for Treating Infectious Diseases
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Application of Nanoparticles and Dendrimers for Treating Infectious Diseases

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: 31 May 2024 | Viewed by 11724

Special Issue Editors

Dr. Carla Zannella

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Guest Editor
Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
Interests: antiviral peptides; viral glycoproteins; dendrimer; natural extracts
Special Issues, Collections and Topics in MDPI journals
Dr. Anna De Filippis

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Guest Editor
Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
Interests: antimicrobial; bacteria; dendrimer; infectious diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The COVID-19 pandemic has stressed the relevance of emerging and reemerging infectious diseases which constantly represent a serious concern not only for their consequences on public health, but also for their economic, social, and political impact around the world. In addition, the diffusion of multi-resistant bacteria and the insufficiency of antiviral drugs emphasize the search for innovative therapeutic strategies able to eradicate bacterial, viral, parasitic, or fungal infections. Nanoparticles and dendrimers are very interesting platforms used as a drug delivery system in various medical fields. This Special Issue aims to collect original and review contributions that deepen the most recent results on the applications of nanoparticles and dendrimers as anti-infective agents with a special focus on their rational design, modification, and the study of their interaction with target pathogens, including bacteria, viruses, parasites, and fungi. We look forward to receiving your contributions.

Dr. Carla Zannella
Dr. Anna De Filippis
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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

  • dendrimers 
  • infectious diseases 
  • antiviral 
  • antibacterial 
  • antiparasitic 
  • antifungal 
  • nanoparticles

Published Papers (7 papers)

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17 pages, 4020 KiB  
Article
SARS-CoV-2 Fusion Peptide Conjugated to a Tetravalent Dendrimer Selectively Inhibits Viral Infection
by Carla Zannella, Annalisa Chianese, Alessandra Monti, Rosa Giugliano, Maria Vittoria Morone, Francesco Secci, Giuseppina Sanna, Aldo Manzin, Anna De Filippis, Nunzianna Doti and Massimiliano Galdiero
Pharmaceutics 2023, 15(12), 2791; https://doi.org/10.3390/pharmaceutics15122791 - 17 Dec 2023
Viewed by 1016
Abstract
Fusion is a key event for enveloped viruses, through which viral and cell membranes come into close contact. This event is mediated by viral fusion proteins, which are divided into three structural and functional classes. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [...] Read more.
Fusion is a key event for enveloped viruses, through which viral and cell membranes come into close contact. This event is mediated by viral fusion proteins, which are divided into three structural and functional classes. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein belongs to class I fusion proteins, characterized by a trimer of helical hairpins and an internal fusion peptide (FP), which is exposed once fusion occurs. Many efforts have been directed at finding antivirals capable of interfering with the fusion mechanism, mainly by designing peptides on the two heptad-repeat regions present in class I viral fusion proteins. Here, we aimed to evaluate the anti-SARS-CoV-2 activity of the FP sequence conjugated to a tetravalent dendrimer through a classical organic nucleophilic substitution reaction (SN2) using a synthetic bromoacetylated peptide mimicking the FP and a branched scaffold of poly-L-Lysine functionalized with cysteine residues. We found that the FP peptide conjugated to the dendrimer, unlike the monomeric FP sequence, has virucidal activity by impairing the attachment of SARS-CoV-2 to cells. Furthermore, we found that the peptide dendrimer does not have the same effects on other coronaviruses, demonstrating that it is selective against SARS-CoV-2. Full article
(This article belongs to the Special Issue Application of Nanoparticles and Dendrimers for Treating Infectious Diseases)
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26 pages, 3734 KiB  
Article
Antimicrobial and Antiproliferative Activity of Green Synthesized Silver Nanoparticles Using Bee Bread Extracts
by Adriana Cristina Urcan, Adriana Dalila Criste, Karina Ioana Szanto, Razvan Ștefan, Marius Zahan, Adriana Sebastiana Muscă, Monica Focsan, Ramona Flavia Burtescu and Neli Kinga Olah
Pharmaceutics 2023, 15(7), 1797; https://doi.org/10.3390/pharmaceutics15071797 - 23 Jun 2023
Cited by 1 | Viewed by 1343
Abstract
Bee bread (BB) is a fermented mixture of bee pollen, is rich in proteins, amino acids, fatty acids, polyphenols, flavonoids, as well as other bioactive compounds, and is considered functional food for humans. In this study, we explored an innovative green synthesis of [...] Read more.
Bee bread (BB) is a fermented mixture of bee pollen, is rich in proteins, amino acids, fatty acids, polyphenols, flavonoids, as well as other bioactive compounds, and is considered functional food for humans. In this study, we explored an innovative green synthesis of colloidal silver nanoparticles, using BB extracts as reducing and stabilizing agents. A preliminary chemical characterization of the BB extracts was conducted. The plasmonic response of the as-synthesized silver nanoparticles (BB-AgNPs) was evaluated by UV–Vis spectroscopy, while their hydrodynamic diameter and zeta potential were investigated by dynamic light spectroscopy (DLS). Transmission electron microscopy (TEM) analysis pointed out polydisperse NPs with quasi-spherical shapes. The newly synthesized nanoparticles showed good antioxidant activity against the tested free radicals, DPPH, ABTS•+, and FRAP, the best results being obtained in the case of ABTS•+. BB-AgNPs exhibited good antibacterial activity on the tested Gram-positive and Gram-negative bacterial strains: herein S. aureus, B. cereus, E. faecalis, E. coli, P. aeruginosa, S. enteritidis, and on yeast C. albicans, respectively. The inhibition diameters varied between 7.67 ± 0.59 and 22.21 ± 1.06 mm, while the values obtained for minimum inhibitory concentration varied between 0.39 and 6.25 µg/mL. In vitro antiproliferative activity was tested on colon adenocarcinoma, ATCC HTB-37 cell line, and the results have shown that the green synthetized BB-AgNPs induced a substantial decrease in tumor cell viability in a dose-dependent manner with an IC50 ranging from 24.58 to 67.91 µg/mL. Consequently, more investigation is required to comprehend the processes of the cytotoxicity of AgNPs and develop strategies to mitigate their potentially harmful effects while harnessing their antimicrobial properties. Full article
(This article belongs to the Special Issue Application of Nanoparticles and Dendrimers for Treating Infectious Diseases)
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18 pages, 4463 KiB  
Article
Fabrication of Co-Assembly from Berberine and Tannic Acid for Multidrug-Resistant Bacteria Infection Treatment
by Tingting Zheng, Huan Chen, Chenyang Wu, Jinrui Wang, Mengyao Cui, Hanyi Ye, Yifan Feng, Ying Li and Zhengqi Dong
Pharmaceutics 2023, 15(7), 1782; https://doi.org/10.3390/pharmaceutics15071782 - 21 Jun 2023
Cited by 2 | Viewed by 1505
Abstract
Long-term antibiotic use induces drug resistance in bacteria. This has given rise to the challenge of refractory infections, which have become a global health threat. Berberine (BBR) and tannic acid (TA) from plants exhibit promising antibacterial activities and may overcome antibiotic resistance. However, [...] Read more.
Long-term antibiotic use induces drug resistance in bacteria. This has given rise to the challenge of refractory infections, which have become a global health threat. Berberine (BBR) and tannic acid (TA) from plants exhibit promising antibacterial activities and may overcome antibiotic resistance. However, poor solubility and/or low penetration capability have limited their application. Carrier-free co-assembled nanocomposites composed entirely of BBR and TA exhibit improved or new properties and produce improved efficacy. Herein, we demonstrated that an ordered nanostructure could be spontaneously co-assembled by the solvent evaporation method using the two natural products. These co-assembled berberine–tannic acid nanoparticles (BBR-TA NPs) exhibited the best antibacterial effect compared with the corresponding physical mixture, pristine BBR, and some first-line antibiotics (benzylpenicillin potassium-BP and ciprofloxacin-Cip) against Staphylococcus aureus (S. aureus) and multidrug-resistant Staphylococcus aureus (MRSA). Even if the concentration of BBR-TA NPs was as low as 15.63 μg/mL, the antibacterial rate against S. aureus and MRSA was more than 80%. In addition to the synergistic effect of the two compounds, the antibacterial mechanism underlying the nanostructures was that they strongly adhered to the surface of the bacterial cell wall, thereby inducing cell membrane damage and intracellular ATP leakage. Furthermore, the in vivo wound healing effect of BBR-TA NPs was verified using an MRSA wound infection mouse model. The BBR-TA NPs achieved the best efficacy compared with BP and Cip. Moreover, cytotoxic and histopathological evaluations of mice revealed that the nanodrug had good biological safety. This facile and green co-assembly strategy for preparing nanoparticles provides a feasible reference for the clinical treatment of bacterial infection. Full article
(This article belongs to the Special Issue Application of Nanoparticles and Dendrimers for Treating Infectious Diseases)
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18 pages, 7008 KiB  
Article
Antiviral Peptides Delivered by Chitosan-Based Nanoparticles to Neutralize SARS-CoV-2 and HCoV-OC43
by Avinash Mali, Gianluigi Franci, Carla Zannella, Annalisa Chianese, Shubaash Anthiya, Ana M. López-Estévez, Alessandra Monti, Anna De Filippis, Nunzianna Doti, María José Alonso and Massimiliano Galdiero
Pharmaceutics 2023, 15(6), 1621; https://doi.org/10.3390/pharmaceutics15061621 - 30 May 2023
Cited by 2 | Viewed by 1644
Abstract
The COVID-19 pandemic has made it clear that there is a crucial need for the design and development of antiviral agents that can efficiently reduce the fatality rate caused by infectious diseases. The fact that coronavirus mainly enters through the nasal epithelial cells [...] Read more.
The COVID-19 pandemic has made it clear that there is a crucial need for the design and development of antiviral agents that can efficiently reduce the fatality rate caused by infectious diseases. The fact that coronavirus mainly enters through the nasal epithelial cells and spreads through the nasal passage makes the nasal delivery of antiviral agents a promising strategy not only to reduce viral infection but also its transmission. Peptides are emerging as powerful candidates for antiviral treatments, showing not only a strong antiviral activity, but also improved safety, efficacy, and higher specificity against viral pathogens. Based on our previous experience on the use of chitosan-based nanoparticles to deliver peptides intra-nasally the current study aimed to explore the delivery of two-novel antiviral peptides making use of nanoparticles consisting of HA/CS and DS/CS. The antiviral peptides were chemically synthesized, and the optimal conditions for encapsulating them were selected through a combination of physical entrapment and chemical conjugation using HA/CS and DS/CS nanocomplexes. Finally, we evaluated the in vitro neutralization capacity against SARS-CoV-2 and HCoV-OC43 for potential use as prophylaxis or therapy. Full article
(This article belongs to the Special Issue Application of Nanoparticles and Dendrimers for Treating Infectious Diseases)
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16 pages, 2210 KiB  
Article
The Novel Synthetic Antibiotic BDTL049 Based on a Dendritic System Induces Lipid Domain Formation while Escaping the Cell Envelope Stress Resistance Determinants
by Philipp F. Popp, Tania Lozano-Cruz, Franziska Dürr, Addis Londaitsbehere, Johanna Hartig, Francisco Javier de la Mata, Rafael Gómez, Thorsten Mascher and Ainhoa Revilla-Guarinos
Pharmaceutics 2023, 15(1), 297; https://doi.org/10.3390/pharmaceutics15010297 - 16 Jan 2023
Viewed by 1409
Abstract
The threat of antimicrobial-resistant bacteria is ever increasing and over the past-decades development of novel therapeutic counter measurements have virtually come to a halt. This circumstance calls for interdisciplinary approaches to design, evaluate and validate the mode of action of novel antibacterial compounds. [...] Read more.
The threat of antimicrobial-resistant bacteria is ever increasing and over the past-decades development of novel therapeutic counter measurements have virtually come to a halt. This circumstance calls for interdisciplinary approaches to design, evaluate and validate the mode of action of novel antibacterial compounds. Hereby, carbosilane dendritic systems that exhibit antimicrobial properties have the potential to serve as synthetic and rationally designed molecules for therapeutic use. The bow-tie type topology of BDTL049 was recently investigated against the Gram-positive model organism Bacillus subtilis, revealing strong bactericidal properties. In this study, we follow up on open questions concerning the usability of BDTL049. For this, we synthesized a fluorescent-labeled version of BDTL049 that maintained all antimicrobial features to unravel the interaction of the compound and bacterial membrane. Subsequently, we highlight the bacterial sensitivity against BDTL049 by performing a mutational study of known resistance determinants. Finally, we address the cytotoxicity of the compound in human cells, unexpectedly revealing a high sensitivity of the eukaryotic cells upon BDTL049 exposure. The insights presented here further elaborate on the unique features of BDTL049 as a promising candidate as an antimicrobial agent while not precluding that further rounds of rational designing are needed to decrease cytotoxicity to ultimately pave the way for synthetic antibiotics toward clinical applicability. Full article
(This article belongs to the Special Issue Application of Nanoparticles and Dendrimers for Treating Infectious Diseases)
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21 pages, 4215 KiB  
Article
Antimicrobial Applications of Green Synthesized Bimetallic Nanoparticles from Ocimum basilicum
by Pragati Rajendra More, Carla Zannella, Veronica Folliero, Francesco Foglia, Romualdo Troisi, Alessandro Vergara, Gianluigi Franci, Anna De Filippis and Massimiliano Galdiero
Pharmaceutics 2022, 14(11), 2457; https://doi.org/10.3390/pharmaceutics14112457 - 14 Nov 2022
Cited by 11 | Viewed by 2039
Abstract
Antibiotic resistance is an important and emerging alarm for public health that requires development of new potential antibacterial strategies. In recent years, nanoscale materials have emerged as an alternative way to fight pathogens. Many researchers have shown great interest in nanoparticles (NPs) using [...] Read more.
Antibiotic resistance is an important and emerging alarm for public health that requires development of new potential antibacterial strategies. In recent years, nanoscale materials have emerged as an alternative way to fight pathogens. Many researchers have shown great interest in nanoparticles (NPs) using noble metals, such as silver, gold, and platinum, even though numerous nanomaterials have shown toxicity. To overcome the problem of toxicity, nanotechnology merged with green chemistry to synthesize nature-friendly nanoparticles from plants. Here, we describe the synthesis of NPs using silver (AgNPs) and platinum (PtNPs) alone or in combination (AgPtNPs) in the presence of Ocimum basilicum (O. basilicum) leaf extract. O. basilicum is a well-known medicinal plant with antibacterial compounds. A preliminary chemical–physical characterization of the extract was conducted. The size, shape and elemental analysis were carried out using UV–Visible spectroscopy, dynamic light scattering (DLS), and zeta potential. Transmission electron microscopy (TEM) confirmed polydisperse NPs with spherical shape. The size of the particles was approximately 59 nm, confirmed by DLS analysis, and the polydisperse index was 0.159. Fourier transform infrared (FTIR) demonstrated an effective and selective capping of the phytoconstituents on the NPs. The cytotoxic activities of AgNPs, PtNPs and AgPtNPs were assessed on different epithelial cell models, using the 3-[4.5-dimethylthiazol-2-yl]-2.5-diphenyltetrazolium bromide (MTT) cell proliferation assay, and discovered low toxicity, with a cell viability of 80%. The antibacterial potential of the NPs was evaluated against Escherichia coli (E. coli), Enterococcus faecalis (E. faecalis), Klebsiella pneumonia (K. pneumoniae), and Staphylococcus aureus (S. aureus) strains. Minimum inhibitory concentration (MIC) assays showed AgPtNP activity till the least concentration of NPs (3.15–1.56 µg/mL) against ATCC, MS, and MDR E. coli, E. faecalis, and S. aureus and the Kirby–Bauer method showed that AgPtNPs gave a zone of inhibition for Gram-positive and Gram-negative bacteria in a range of 9–25 mm. In addition, we obtained AgPtNP synergistic activity in combination with vancomycin or ampicillin antibiotics. Taken together, these results indicate that bimetallic nanoparticles, synthesized from O. basilicum leaf extract, could represent a natural, ecofriendly, cheap, and safe method to produce alternative antibacterial strategies with low cytotoxicity. Full article
(This article belongs to the Special Issue Application of Nanoparticles and Dendrimers for Treating Infectious Diseases)
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15 pages, 2006 KiB  
Systematic Review
Antibacterial Properties of Gold Nanoparticles in the Modification of Medical Implants: A Systematic Review
by Xinxin Zhan, Jianglong Yan, Hao Tang, Dandan Xia and Hong Lin
Pharmaceutics 2022, 14(12), 2654; https://doi.org/10.3390/pharmaceutics14122654 - 30 Nov 2022
Cited by 10 | Viewed by 1823
Abstract
The widespread occurrence of bacterial infections and their increased resistance to antibiotics has led to the development of antimicrobial coatings for multiple medical implants. Owing to their desirable properties, gold nanoparticles (AuNPs) have been developed as antibacterial agents. This systematic investigation sought to [...] Read more.
The widespread occurrence of bacterial infections and their increased resistance to antibiotics has led to the development of antimicrobial coatings for multiple medical implants. Owing to their desirable properties, gold nanoparticles (AuNPs) have been developed as antibacterial agents. This systematic investigation sought to analyze the antibacterial effects of implant material surfaces modified with AuNPs. The data from 27 relevant studies were summed up. The included articles were collected from September 2011 to September 2021. According to the retrieved literature, we found that medical implants modified by AuNPs have good antibacterial effects against gram-positive and gram-negative bacteria, and the antibacterial effects would be improved by near-infrared (NIR) radiation. Full article
(This article belongs to the Special Issue Application of Nanoparticles and Dendrimers for Treating Infectious Diseases)
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