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Pharmaceutics
Special Issues
Antimicrobial Sonodynamic and Photodynamic Therapies
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Antimicrobial Sonodynamic and Photodynamic Therapies

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

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 10674

Special Issue Editors

Dr. Ewerton Garcia De Oliveira Mima

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Guest Editor
Laboratory of Applied Microbiology, Department of Dental Materials and Prosthodontics, School of Dentistry, São Paulo State University (Unesp), Araraquara 14800-000, Brazil
Interests: antifungal drug resistance; photodynamic therapy; oral microbiology; biofilms; fungal infections
Prof. Dr. Ana Claudia Pavarina

E-Mail Website
Guest Editor
Laboratory of Applied Microbiology, Department of Dental Materials and Prosthodontics, School of Dentistry, São Paulo State University (UNESP), Araraquara 14801-903, Brazil
Interests: photodynamic therapy; prosthetic stomatitis; oral biofilm; antifungals
Dr. Livia Nordi Dovigo

E-Mail Website
Guest Editor
Department of Social Dentistry, School of Dentistry, São Paulo State University (UNESP), Rua Humaitá 1680, Araraquara SP 14801-903, Brazil
Interests: photodynamic inactivation; oral biofilms; antifungal drug resistance; curcumin; systematic reviews; research methods and proper study design

Special Issue Information

Dear Colleagues,

Global changes have influenced the existing infectious diseases, such as vector-borne illness, and the emergence of new pathogens, which may result in epidemics and pandemics. Moreover, the overuse of antimicrobial agents (antibiotics and antifungals) has led to the problem of antimicrobial resistance. Multidrug-resistant pathogens are difficult to treat and cause diseases with high morbidity and mortality; sometimes no option of treatment is available. Microbial biofilms are also a challenge, because they require high concentrations of antimicrobials for their inactivation and are responsible for chronic and recurrent diseases. Therefore, the development of alternative therapies is encouraged, and antimicrobial photodynamic and sonodynamic therapies (aPDT and aSDT) have been studied in the battle against new and/or resistant microbes.

This Special Issue aims to gather recent advances about aPDT and aSDT against pathogens. In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: new photosensitizers (PS) and formulations, biofilms, combination therapy, cell biology, molecular biology, biophotonics, oxidative stress, and virulence.

We look forward to receiving your contributions.

Dr. Ewerton Garcia De Oliveira Mima
Prof. Dr. Ana Claudia Pavarina
Dr. Livia Nordi Dovigo
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

  • photochemotherapy
  • anti-infective agents
  • biofilms
  • drug resistance
  • light
  • ultrasonics
  • combined modality therapy

Published Papers (6 papers)

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Research

17 pages, 3767 KiB  
Article
The First Report of In Vitro Antifungal and Antibiofilm Photodynamic Activity of Tetra-Cationic Porphyrins Containing Pt(II) Complexes against Candida albicans for Onychomycosis Treatment
by Ticiane da Rosa Pinheiro, Gabrielle Aguiar Dantas, Jean Lucas Gutknecht da Silva, Daniela Bitencourt Rosa Leal, Ricardo Barreto da Silva, Thiago Augusto de Lima Burgo, Roberto Christ Vianna Santos and Bernardo Almeida Iglesias
Pharmaceutics 2023, 15(5), 1511; https://doi.org/10.3390/pharmaceutics15051511 - 16 May 2023
Cited by 1 | Viewed by 1597
Abstract
Onychomycosis is a prevalent nail fungal infection, and Candida albicans is one of the most common microorganisms associated with it. One alternative therapy to the conventional treatment of onychomycosis is antimicrobial photoinactivation. This study aimed to evaluate for the first time the in [...] Read more.
Onychomycosis is a prevalent nail fungal infection, and Candida albicans is one of the most common microorganisms associated with it. One alternative therapy to the conventional treatment of onychomycosis is antimicrobial photoinactivation. This study aimed to evaluate for the first time the in vitro activity of cationic porphyrins with platinum(II) complexes 4PtTPyP and 3PtTPyP against C. albicans. The minimum inhibitory concentration of porphyrins and reactive oxygen species was evaluated by broth microdilution. The yeast eradication time was evaluated using a time-kill assay, and a checkerboard assay assessed the synergism in combination with commercial treatments. In vitro biofilm formation and destruction were observed using the crystal violet technique. The morphology of the samples was evaluated by atomic force microscopy, and the MTT technique was used to evaluate the cytotoxicity of the studied porphyrins in keratinocyte and fibroblast cell lines. The porphyrin 3PtTPyP showed excellent in vitro antifungal activity against the tested C. albicans strains. After white-light irradiation, 3PtTPyP eradicated fungal growth in 30 and 60 min. The possible mechanism of action was mixed by ROS generation, and the combined treatment with commercial drugs was indifferent. The 3PtTPyP significantly reduced the preformed biofilm in vitro. Lastly, the atomic force microscopy showed cellular damage in the tested samples, and 3PtTPyP did not show cytotoxicity against the tested cell lines. We conclude that 3PtTPyP is an excellent photosensitizer with promising in vitro results against C. albicans strains. Full article
(This article belongs to the Special Issue Antimicrobial Sonodynamic and Photodynamic Therapies)
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16 pages, 31814 KiB  
Article
Photodynamic Inhibition of Herpes Simplex Virus 1 Infection by Tricationic Amphiphilic Porphyrin with a Long Alkyl Chain
by Igor Jurak, Maja Cokarić Brdovčak, Lara Djaković, Ivana Bertović, Klaudia Knežević, Martin Lončarić, Antonija Jurak Begonja and Nela Malatesti
Pharmaceutics 2023, 15(3), 956; https://doi.org/10.3390/pharmaceutics15030956 - 15 Mar 2023
Cited by 2 | Viewed by 1605
Abstract
Photodynamic therapy (PDT) is broadly used to treat different tumors, and it is a rapidly developing approach to inactivating or inhibiting the replication of fungi, bacteria, and viruses. Herpes simplex virus 1 (HSV-1) is an important human pathogen and a frequently used model [...] Read more.
Photodynamic therapy (PDT) is broadly used to treat different tumors, and it is a rapidly developing approach to inactivating or inhibiting the replication of fungi, bacteria, and viruses. Herpes simplex virus 1 (HSV-1) is an important human pathogen and a frequently used model to study the effects of PDT on enveloped viruses. Although many photosensitizers (PSs) have been tested for their antiviral properties, analyses are usually limited to assessing the reduction in viral yield, and thus the molecular mechanisms of photodynamic inactivation (PDI) remain poorly understood. In this study, we investigated the antiviral properties of TMPyP3-C17H35, a tricationic amphiphilic porphyrin-based PS with a long alkyl chain. We show that light-activated TMPyP3-C17H35 can efficiently block virus replication at certain nM concentrations without exerting obvious cytotoxicity. Moreover, we show that the levels of viral proteins (immediate-early, early, and late genes) were greatly reduced in cells treated with subtoxic concentrations of TMPyP3-C17H35, resulting in markedly decreased viral replication. Interestingly, we observed a strong inhibitory effect of TMPyP3-C17H35 on the virus yield only when cells were treated before or shortly after infection. In addition to the antiviral activity of the internalized compound, we show that the compound dramatically reduces the infectivity of free virus in the supernatant. Overall, our results demonstrate that activated TMPyP3-C17H35 effectively inhibits HSV-1 replication and that it can be further developed as a potential novel treatment and used as a model to study photodynamic antimicrobial chemotherapy. Full article
(This article belongs to the Special Issue Antimicrobial Sonodynamic and Photodynamic Therapies)
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17 pages, 2251 KiB  
Article
Tuning the Molecular Structure of Corroles to Enhance the Antibacterial Photosensitizing Activity
by Edwin J. Gonzalez Lopez, Sol R. Martínez, Virginia Aiassa, Sofía C. Santamarina, Rodrigo E. Domínguez, Edgardo N. Durantini and Daniel A. Heredia
Pharmaceutics 2023, 15(2), 392; https://doi.org/10.3390/pharmaceutics15020392 - 24 Jan 2023
Cited by 1 | Viewed by 1489
Abstract
The increase in the antibiotic resistance of bacteria is a serious threat to public health. Photodynamic inactivation (PDI) of micro-organisms is a reliable antimicrobial therapy to treat a broad spectrum of complex infections. The development of new photosensitizers with suitable properties is a [...] Read more.
The increase in the antibiotic resistance of bacteria is a serious threat to public health. Photodynamic inactivation (PDI) of micro-organisms is a reliable antimicrobial therapy to treat a broad spectrum of complex infections. The development of new photosensitizers with suitable properties is a key factor to consider in the optimization of this therapy. In this sense, four corroles were designed to study how the number of cationic centers can influence the efficacy of antibacterial photodynamic treatments. First, 5,10,15-Tris(pentafluorophenyl)corrole (Co) and 5,15-bis(pentafluorophenyl)-10-(4-(trifluoromethyl)phenyl)corrole (Co-CF3) were synthesized, and then derivatized by nucleophilic aromatic substitution with 2-dimethylaminoethanol and 2-(dimethylamino)ethylamine, obtaining corroles Co-3NMe2 and Co-CF3-2NMe2, respectively. The straightforward synthetic strategy gave rise to macrocycles with different numbers of tertiary amines that can acquire positive charges in an aqueous medium by protonation at physiological pH. Spectroscopic and photodynamic studies demonstrated that their properties as chromophores and photosensitizers were unaffected, regardless of the substituent groups on the periphery. All tetrapyrrolic macrocycles were able to produce reactive oxygen species (ROS) by both photodynamic mechanisms. Uptake experiments, the level of ROS produced in vitro, and PDI treatments mediated by these compounds were assessed against clinical strains: methicillin-resistant Staphylococcus aureus and Klebsiella pneumoniae. In vitro experiments indicated that the peripheral substitution significantly affected the uptake of the photosensitizers by microbes and, consequently, the photoinactivation performance. Co-3NMe2 was the most effective in killing both Gram-positive and Gram-negative bacteria (inactivation > 99.99%). This work lays the foundations for the development of new corrole derivatives having pH-activable cationic groups and with plausible applications as effective broad-spectrum antimicrobial photosensitizers. Full article
(This article belongs to the Special Issue Antimicrobial Sonodynamic and Photodynamic Therapies)
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20 pages, 5843 KiB  
Article
Effect of Solubilizing Group on the Antibacterial Activity of Heptamethine Cyanine Photosensitizers
by Olga Semenova, Dmytro Kobzev, Iryna Hovor, Melad Atrash, Faina Nakonechny, Olesia Kulyk, Andrii Bazylevich, Gary Gellerman and Leonid Patsenker
Pharmaceutics 2023, 15(1), 247; https://doi.org/10.3390/pharmaceutics15010247 - 11 Jan 2023
Cited by 3 | Viewed by 1496
Abstract
Antibiotic resistance of pathogenic bacteria dictates the development of novel treatment modalities such as antimicrobial photodynamic therapy (APDT) utilizing organic dyes termed photosensitizers that exhibit a high cytotoxicity upon light irradiation. Most of the clinically approved photosensitizers are porphyrins that are poorly excitable [...] Read more.
Antibiotic resistance of pathogenic bacteria dictates the development of novel treatment modalities such as antimicrobial photodynamic therapy (APDT) utilizing organic dyes termed photosensitizers that exhibit a high cytotoxicity upon light irradiation. Most of the clinically approved photosensitizers are porphyrins that are poorly excitable in the therapeutic near-IR spectral range. In contrast, cyanine dyes function well in the near-IR region, but their phototoxicity, in general, is very low. The introduction of iodine atoms in the cyanine molecules was recently demonstrated to greatly increase their phototoxicity. Herein, we synthesized a series of the new iodinated heptamethine cyanine dyes (ICy7) containing various solubilizing moieties, i.e., negatively charged carboxylic (ICy7COOH) and sulfonic (ICy7SO3H) groups, positively charged triphenylphosphonium (ICy7PPh3), triethylammonium (ICy7NEt3) and amino (ICy7NH2) groups, and neutral amide (ICy7CONHPr) group. The effect of these substituents on the photodynamic eradication of Gram-positive (S. aureus) and Gram-negative (E. coli and P. aeruginosa) pathogens was studied. Cyanine dyes containing the amide and triphenylphosphonium groups were found to be the most efficient for eradication of the investigated bacteria. These dyes are effective at low concentrations of 0.05 µM (33 J/cm2) for S. aureus, 50 µM (200 J/cm2) for E. coli, and 5 µM (100 J/cm2) for P. aeruginosa and considered, therefore, promising photosensitizers for APDT applications. The innovation of the new photosensitizers consisted of a combination of the heavy-atom effect that increases singlet oxygen generation with the solubilizing group’s effect improving cell uptake, and with effective near-IR excitation. Such a combination helped to noticeably increase the APDT efficacy and should pave the way for the development of more advanced photosensitizers for clinical use. Full article
(This article belongs to the Special Issue Antimicrobial Sonodynamic and Photodynamic Therapies)
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16 pages, 2084 KiB  
Article
In Vitro Evaluation of Photodynamic Activity of Plant Extracts from Senna Species against Microorganisms of Medical and Dental Interest
by Analú Barros de Oliveira, Túlio Morandin Ferrisse, Sarah Raquel de Annunzio, Maria Gleiziane Araújo Franca, Maria Goretti de Vasconcelos Silva, Alberto José Cavalheiro, Carla Raquel Fontana and Fernanda Lourenção Brighenti
Pharmaceutics 2023, 15(1), 181; https://doi.org/10.3390/pharmaceutics15010181 - 04 Jan 2023
Cited by 2 | Viewed by 1350
Abstract
Background: Bacterial resistance requires new treatments for infections. In this context, antimicrobial photodynamic therapy (aPDT) is an effective and promising option. Objectives: Three plant extracts (Senna splendida, Senna alata, and Senna macranthera) were evaluated as photosensitizers for aPDT. Methods: [...] Read more.
Background: Bacterial resistance requires new treatments for infections. In this context, antimicrobial photodynamic therapy (aPDT) is an effective and promising option. Objectives: Three plant extracts (Senna splendida, Senna alata, and Senna macranthera) were evaluated as photosensitizers for aPDT. Methods: Cutibacterium acnes (ATCC 6919), Streptococcus mutans (ATCC 35668), Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), and Candida albicans (ATCC 90028) were evaluated. Reactive oxygen species production was also verified. Oral keratinocytes assessed cytotoxicity. LC-DAD-MS analysis identified the chemical components of the evaluated extracts. Results: Most species cultured in the planktonic phase showed total microbial reduction (>6 log10 CFU/mL/p < 0.0001) for all extracts. C. albicans cultured in biofilm showed total microbial reduction (7.68 log10 CFU/mL/p < 0.0001) for aPDT mediated by all extracts. Extracts from S. macranthera and S. alata produced the highest number of reactive oxygen species (p < 0.0001). The S. alata extract had the highest cell viability. The LC-DAD-MS analysis of active extracts showed one naphthopyrone and seven anthraquinones as potential candidates for photoactive compounds. Conclusion: This study showed that aPDT mediated by Senna spp. was efficient in microbial suspension and biofilm of microorganisms of medical and dental interest. Full article
(This article belongs to the Special Issue Antimicrobial Sonodynamic and Photodynamic Therapies)
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19 pages, 1417 KiB  
Article
Zinc(II), Palladium(II), and Metal-Free Phthalocyanines Bearing Nipagin-Functionalized Substituents against Candida auris and Selected Multidrug-Resistant Microbes
by Daniel Ziental, Dariusz T. Mlynarczyk, Emil Kolasinski, Emre Güzel, Jolanta Dlugaszewska, Łukasz Popenda, Stefan Jurga, Tomasz Goslinski and Lukasz Sobotta
Pharmaceutics 2022, 14(8), 1686; https://doi.org/10.3390/pharmaceutics14081686 - 12 Aug 2022
Cited by 9 | Viewed by 2217
Abstract
Due to the rapidly increasing problem of antibiotic resistance in recent years, the use of phthalocyanines as photosensitizers with their superior properties in photodynamic antimicrobial therapy (PACT) applications has become important. In this study, magnesium(II) 1,4,8,11,15,18,22,25-octakis(4-[4-butoxycarbonylphenoxy]butyloxy)phthalocyanine was used in the demetalation reaction in [...] Read more.
Due to the rapidly increasing problem of antibiotic resistance in recent years, the use of phthalocyanines as photosensitizers with their superior properties in photodynamic antimicrobial therapy (PACT) applications has become important. In this study, magnesium(II) 1,4,8,11,15,18,22,25-octakis(4-[4-butoxycarbonylphenoxy]butyloxy)phthalocyanine was used in the demetalation reaction in trifluoroacetic acid, and subsequently subjected to metalation reaction in dimethylformamide with zinc(II) acetate and bis(benzonitrile)palladium(II) chloride towards zinc(II) and palladium(II) derivatives. Three phthalocyanines, including a demetalated one as well as two metalated, in the core with zinc(II) and palladium(II) were characterized using 1D and 2D NMR spectroscopy and mass spectrometry. In addition, all macrocycles were subjected to absorption and emission studies as well as photostability tests. In a photochemical study, zinc(II) and palladium(II) phthalocyanine complexes appeared to be efficient singlet oxygen generators. There were noted quantum yields of singlet oxygen generation for zinc(II) phthalocyanine derivative in DMF and DMSO at 0.55 and 0.72, whereas for palladium(II) complex at 0.73 and 0.77, respectively. Liposomal formulations of phthalocyanine derivatives were prepared, and their activity was evaluated against a broad spectrum of antibiotic-resistant microorganisms, such as methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli (ESBL+), Candida albicans resistant to fluconazole, C. auris, and against dermatophytes. Phthalocyanine palladium(II) complex showed the highest bactericidal activity against all antibiotic-resistant microorganisms, including reducing C. auris growth at 3.54 log. Full article
(This article belongs to the Special Issue Antimicrobial Sonodynamic and Photodynamic Therapies)
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