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Pharmaceutics
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New Antimicrobial Agents and Non-invasive Drug Delivery Routes: A Look...
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New Antimicrobial Agents and Non-invasive Drug Delivery Routes: A Look into the Future

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

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 9334

Special Issue Editor

Prof. Dr. Victor Manuel Balcão

E-Mail Website
Guest Editor
PhageLab – Laboratory of Biofilms and Bacteriophages, University of Sorocaba, Rodovia Raposo Tavares km 92.5, Vila Artura, Sorocaba CEP 18023-000, São Paulo, Brazil
Interests: structural and functional stabilization of protein entities; bacteriophages; transdermal drug delivery; phage-based biocontrol
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Over the past few years, worldwide bacterial resistance to chemical antibiotics has increased dramatically and reached a “new pre-antibiotic era”, in such a high level that endangers public health. According to the World Alliance Against Antibiotic Resistance (WAAAR), antibiotics may completely lose their effectiveness in only a few years due to a combination of both self-medication and irrational prescription and use of these therapeutic agents, as well as due to their extensive use in agriculture, aquaculture and veterinary practice. This has led to the development of multi-resistant bacterial strains, and in fact, some of them are resistant to all currently available antibiotics. Hence, the need to develop feasible alternatives to antibiotics becomes more and more of utmost importance, so as to protect and promote global public health. Several (potential) alternative (or complement) antimicrobial strategies to current chemical antibiotics are under investigation, such as bacteriophage therapy (making use of strictly lytic phage particles), (recombinant) lysin therapy (at nanogram-scale, for infections caused by Gram-positive bacteria), antimicrobial peptides (amphiphilic polypeptides that disrupt the bacterial membrane), antimicrobial photodynamic therapy (aPDT, requiring the combination of a photosensitizer, visible light and molecular oxygen to produce reactive oxygen species that cause irreversible damages in microorganisms; due to the multitarget nature of aPDT, development of bacterial resistance is virtually nil). Additionally, the use of antibacterial antibodies promises to be extremely safe and effective, and vaccination emerges as one of the most promising preventive strategies. In addition, innovative non-invasive drug-delivery strategies for new antimicrobials, such as transdermal permeation, have the potential to circumvent the drawbacks associated with both enteric or parenteric administration, and have started to be studied by several researchers, revealing that this administration route may be worthy of further investigation. For instance, transdermal permeation of bacteriophage particles or other antimicrobial moieties has been successfully exploited in attempts to eradicate resistant chronic infections. This Special Issue aims to collect original contributions (research articles and reviews) describing and reporting recent advances and developments in the field of new antimicrobial strategies and non-invasive drug-delivery routes, either laboratory studies or clinical applications.

Potential topics include, but are not limited to:

  • strictly lytic bacteriophage particles
  • antimicrobial photodynamic therapy
  • design and synthesis of innovative antibacterial agents
  • recombinant lysin therapy
  • antimicrobial peptides
  • antibacterial antibodies
  • non-invasive strategies for antibacterial drug delivery
  • mechanisms involved in the development of bacterial resistance
  • resistance to bacteriophages
  • mucosal delivery
  • transdermal permeation

Prof. Dr. Victor M. Balcão
Guest Editor

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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

  • strictly lytic bacteriophage particles
  • antimicrobial photodynamic therapy
  • design and synthesis of innovative antibacterial agents
  • recombinant lysin therapy
  • antimicrobial peptides
  • antibacterial antibodies
  • non-invasive strategies for antibacterial drug delivery
  • mechanisms involved in the development of bacterial resistance
  • resistance to bacteriophages
  • mucosal delivery
  • transdermal permeation

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Published Papers (3 papers)

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Research

14 pages, 1875 KiB  
Article
Antimicrobial and Toxicity Evaluation of Imidazolium-Based Dicationic Ionic Liquids with Dicarboxylate Anions
by Bruna L. Kuhn, Taís F. A. Kaminski, Ânderson R. Carvalho, Alexandre M. Fuentefria, Bianca M. B. C. Johann, Edilma E. da Silva, Gustavo P. Silveira, Tássia L. da Silveira, Félix A. A. Soares, Nilo Zanatta and Clarissa P. Frizzo
Pharmaceutics 2021, 13(5), 639; https://doi.org/10.3390/pharmaceutics13050639 - 29 Apr 2021
Cited by 12 | Viewed by 2272
Abstract
Imidazolium-based dicationic ILs (DILs) presenting antimicrobial activity and relatively low toxicity are highly desirable and are envisioned for use in live tissue to prevent bacterial or fungal infections. In this context, we present here DILs with dicarboxylate anions [Cn(MIM)2[C [...] Read more.
Imidazolium-based dicationic ILs (DILs) presenting antimicrobial activity and relatively low toxicity are highly desirable and are envisioned for use in live tissue to prevent bacterial or fungal infections. In this context, we present here DILs with dicarboxylate anions [Cn(MIM)2[Cn(MIM)2][CO2-(CH2)mCO2], in which n = 4, 6, 8, and 10, and m = 0, 1, 2, 3, 4, and 5. The results showed that DILs with an alkyl chain spacer of ten carbons were active against yeasts and the bacterial strains tested. However, most of the DILs were cytotoxic and toxic at 1 mM. By contrast, DILs with alkyl chains possessing less than ten carbons were active against some specific Candidas and bacteria (mainly S. aureus), and they showed moderate cytotoxicity. The best activity against Gram-positive bacteria was observed for [C4(MIM)2][Pim] toward MRSA. For the DILs described herein, their level of toxicity against C. elegans was lower than that of most of the mono- and dicationic IL analogs with other anions. Our results showed that the presence of carboxylate anions reduces the toxicity of DILs compared to DILs containing halide anions, which is particularly significant to the means of designing biologically active compounds in antimicrobial formulations. Full article
(This article belongs to the Special Issue New Antimicrobial Agents and Non-invasive Drug Delivery Routes: A Look into the Future)
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13 pages, 5263 KiB  
Article
Performance of Choline Geranate Deep Eutectic Solvent as Transdermal Permeation Enhancer: An In Vitro Skin Histological Study
by Rodrigo Boscariol, Érika A. Caetano, Erica C. Silva, Thais J. Oliveira, Raquel M. Rosa-Castro, Marta M. D. C. Vila and Victor M. Balcão
Pharmaceutics 2021, 13(4), 540; https://doi.org/10.3390/pharmaceutics13040540 - 13 Apr 2021
Cited by 21 | Viewed by 3625
Abstract
In the present research work, we addressed the changes in skin by which deep eutectic solvents (DES) enhanced transdermal permeation of bioactive compounds and propose a rationale for this mechanism. Several studies showed that these unusual liquids were ideal solvents for transdermal delivery [...] Read more.
In the present research work, we addressed the changes in skin by which deep eutectic solvents (DES) enhanced transdermal permeation of bioactive compounds and propose a rationale for this mechanism. Several studies showed that these unusual liquids were ideal solvents for transdermal delivery of biomolecules, but to date, no histological studies relating the action of DES to changes in the structure of the outer skin barrier have been reported. In the research effort described herein, we presented an in-depth analysis of the changes induced in the skin by choline geranate DES, a compound with proven capabilities of enhancing transdermal permeation without deleterious impacts on the cells. The results obtained showed that a low percentage of DES acted as a transient disruptor of the skin structure, facilitating the passage of bioactive compounds dissolved in it. Full article
(This article belongs to the Special Issue New Antimicrobial Agents and Non-invasive Drug Delivery Routes: A Look into the Future)
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18 pages, 3233 KiB  
Article
Amphipathic Peptide Antibiotics with Potent Activity against Multidrug-Resistant Pathogens
by Jingru Shi, Chen Chen, Dejuan Wang, Ziwen Tong, Zhiqiang Wang and Yuan Liu
Pharmaceutics 2021, 13(4), 438; https://doi.org/10.3390/pharmaceutics13040438 - 24 Mar 2021
Cited by 21 | Viewed by 2903
Abstract
The emergence and prevalence of multidrug-resistant (MDR) bacteria have posed a serious threat to public health. Of particular concern are methicillin-resistant Staphylococcus aureus (MRSA) and blaNDM, mcr-1 and tet(X)-positive Gram-negative pathogens. The fact that few new antibiotics have been approved [...] Read more.
The emergence and prevalence of multidrug-resistant (MDR) bacteria have posed a serious threat to public health. Of particular concern are methicillin-resistant Staphylococcus aureus (MRSA) and blaNDM, mcr-1 and tet(X)-positive Gram-negative pathogens. The fact that few new antibiotics have been approved in recent years exacerbates this global crisis, thus, new alternatives are urgently needed. Antimicrobial peptides (AMPs) originated from host defense peptides with a wide range of sources and multiple functions, are less prone to achieve resistance. All these characteristics laid the foundation for AMPs to become potential antibiotic candidates. In this study, we revealed that peptide WW307 displayed potent antibacterial and bactericidal activity against MDR bacteria, including MRSA and Gram-negative bacteria carrying blaNDM-5, mcr-1 or tet(X4). In addition, WW307 exhibited great biofilm inhibition and eradication activity. Safety and stability experiments showed that WW307 had a strong resistance against various physiological conditions and displayed relatively low toxicity. Mechanistic experiments showed that WW307 resulted in membrane damage by selectively targeting bacterial membrane-specific components, including lipopolysaccharide (LPS), phosphatidylglycerol (PG), and cardiolipin (CL). Moreover, WW307 dissipated membrane potential and triggered the production of reactive oxygen species (ROS). Collectively, these results demonstrated that WW307 represents a promising candidate for combating MDR pathogens. Full article
(This article belongs to the Special Issue New Antimicrobial Agents and Non-invasive Drug Delivery Routes: A Look into the Future)
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