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Special Issue in Honor of Dr. Michael Weber’s 70th Birthday:...
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Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications

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

Deadline for manuscript submissions: closed (20 December 2021) | Viewed by 93471

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Prof. Dr. Udo Bakowsky

E-Mail Website
Guest Editor
Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch-Str. 4, 35037 Marburg, Germany
Interests: nanoscale drug delivery systems; photodynamic therapy; liposomes; gene therapy
Special Issues, Collections and Topics in MDPI journals
Dr. Matthias Wojcik

E-Mail Website
Guest Editor
Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch-Str. 4, 35037 Marburg, Germany
Interests: photodynamic therapy; drug delivery systems; nanoscale drug carriers
Dr. Eduard Preis

E-Mail Website
Guest Editor
Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch-Str. 4, 35037 Marburg, Germany
Interests: photodynamic therapy; antimicrobial therapy; nanofibers; polymeric nanoparticles
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Gerhard Litscher

E-Mail Website1 Website2
Co-Guest Editor
High-Tech Acupuncture and Digital Chinese Medicine, Swiss University of Traditional Chinese Medicine, 5330 Bad Zurzach, Switzerland
Interests: photobiomodulation; laser therapy; laser acupuncture; laser medicine; evidence-based complementary medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This commemorative Special Issue of Pharmaceutics is in honor of Dr. Michael Weber and his 70th birthday. Dr. Michael Weber is an internationally recognized medical practitioner and scientist in the field of photodynamic therapy and application of lasers.

Despite his work as a practicing doctor, Dr. Michael Weber has published many papers in the field of laser application. The laser devices invented and patented by Michael Weber have also been used by other scientists in many publications dealing with topical and interstitial photodynamic therapy. He is the founder of the International Society for Medical Laser Applications (ISLA) which combines the proficiencies of many honorable scientists all around the world. Dr. Weber has received different funding by the German government and the European Union for research development. He is also the host of three annual conferences (in Europe, Asia, and America) on the subject of photodynamic therapy and laser application.

He has pioneered the clinical use of lasers and photodynamic therapy for nearly 25 years in Germany and several other countries. Most recently, Dr. Weber’s research on the photodynamic killing of viruses and microorganisms, conducted in an international cooperation, successfully resulted in a published study using Riboflavin (Vitamin B2) and UV-light.

In honor and recognition of Dr. Michael Weber’s outstanding contributions to this field, this Special Issue welcomes the submission of original research manuscripts or reviews in the area of pharmaceutical sciences. We plan to receive submissions from now to July 20, 2021. Manuscripts will be published online on an ongoing basis after being processed.

Prof. Dr. Udo Bakowsky
Dr. Matthias Wojcik
Dr. Eduard Preis
Prof. Dr. Gerhard Litscher
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

  • photodynamic therapy and its application
  • all applications of PDT, e.g.
  • PDT in tumor therapy
  • PDT in antimicrobial therapy
  • PDT in combination with other types of therapy, e.g.
  • classical chemotherapy
  • antibiotics
  • stem-cell therapy
  • radiation therapy
  • ultrasound applications
  • photothermal therapy (PTT)
  • physicochemical characterization of new carriers for PDT
  • antimicrobial PDT for viral infections (including COVID-19)
  • antimicrobial PDT and biofilms
  • antimicrobial PDT for chronic wounds
  • new photosensitizers and their effects
  • clinical applications of PDT
  • drug delivery systems
  • new carrier systems for PDT, e.g.
  • liposomes
  • micelles
  • nanoparticles
  • fibers
  • nanorods

Related Special Issue

Published Papers (26 papers)

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Editorial

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4 pages, 202 KiB  
Editorial
Editorial on the “Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications”
by Eduard Preis, Matthias Wojcik, Gerhard Litscher and Udo Bakowsky
Pharmaceutics 2022, 14(9), 1786; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14091786 - 26 Aug 2022
Cited by 2 | Viewed by 1208
Abstract
Thousands of years ago, phototherapy or heliotherapy was performed by ancient Egyptians, Greeks, and Romans [...] Full article
(This article belongs to the Special Issue Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications)

Research

Jump to: Editorial, Review

26 pages, 23422 KiB  
Article
Broad-Spectrum Antimicrobial ZnMintPc Encapsulated in Magnetic-Nanocomposites with Graphene Oxide/MWCNTs Based on Bimodal Action of Photodynamic and Photothermal Effects
by Coralia Fabiola Cuadrado, Antonio Díaz-Barrios, Kleber Orlando Campaña, Eric Cardona Romani, Francisco Quiroz, Stefania Nardecchia, Alexis Debut, Karla Vizuete, Dario Niebieskikwiat, Camilo Ernesto Ávila, Mateo Alejandro Salazar, Cristina Garzón-Romero, Ailín Blasco-Zúñiga, Miryan Rosita Rivera and María Paulina Romero
Pharmaceutics 2022, 14(4), 705; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14040705 - 26 Mar 2022
Cited by 11 | Viewed by 3407
Abstract
Microbial diseases have been declared one of the main threats to humanity, which is why, in recent years, great interest has been generated in the development of nanocomposites with antimicrobial capacity. The present work studied two magnetic nanocomposites based on graphene oxide (GO) [...] Read more.
Microbial diseases have been declared one of the main threats to humanity, which is why, in recent years, great interest has been generated in the development of nanocomposites with antimicrobial capacity. The present work studied two magnetic nanocomposites based on graphene oxide (GO) and multiwall carbon nanotubes (MWCNTs). The synthesis of these magnetic nanocomposites consisted of three phases: first, the synthesis of iron magnetic nanoparticles (MNPs), second, the adsorption of the photosensitizer menthol-Zinc phthalocyanine (ZnMintPc) into MWCNTs and GO, and the third phase, encapsulation in poly (N-vinylcaprolactam-co-poly(ethylene glycol diacrylate)) poly (VCL-co-PEGDA) polymer VCL/PEGDA a biocompatible hydrogel, to obtain the magnetic nanocomposites VCL/PEGDA-MNPs-MWCNTs-ZnMintPc and VCL/PEGDA-MNPs-GO-ZnMintPc. In vitro studies were carried out using Escherichia coli and Staphylococcus aureus bacteria and the Candida albicans yeast based on the Photodynamic/Photothermal (PTT/PDT) effect. This research describes the nanocomposites’ optical, morphological, magnetic, and photophysical characteristics and their application as antimicrobial agents. The antimicrobial effect of magnetics nanocomposites was evaluated based on the PDT/PTT effect. For this purpose, doses of 65 mW·cm−2 with 630 nm light were used. The VCL/PEGDA-MNPs-GO-ZnMintPc nanocomposite eliminated E. coli and S. aureus colonies, while the VCL/PEGDA-MNPs-MWCNTs-ZnMintPc nanocomposite was able to kill the three types of microorganisms. Consequently, the latter is considered a broad-spectrum antimicrobial agent in PDT and PTT. Full article
(This article belongs to the Special Issue Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications)
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15 pages, 2867 KiB  
Article
Study of Viral Photoinactivation by UV-C Light and Photosensitizer Using a Pseudotyped Model
by Mohammad Sadraeian, Fabio Francisco Pinto Junior, Marcela Miranda, Juliana Galinskas, Rafaela Sachetto Fernandes, Edgar Ferreira da Cruz, Libing Fu, Le Zhang, Ricardo Sobhie Diaz, Gustavo Cabral-Miranda and Francisco Eduardo Gontijo Guimarães
Pharmaceutics 2022, 14(3), 683; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14030683 - 21 Mar 2022
Cited by 10 | Viewed by 3385
Abstract
Different light-based strategies have been investigated to inactivate viruses. Herein, we developed an HIV-based pseudotyped model of SARS-CoV-2 (SC2) to study the mechanisms of virus inactivation by using two different strategies; photoinactivation (PI) by UV-C light and photodynamic inactivation (PDI) by Photodithazine photosensitizer [...] Read more.
Different light-based strategies have been investigated to inactivate viruses. Herein, we developed an HIV-based pseudotyped model of SARS-CoV-2 (SC2) to study the mechanisms of virus inactivation by using two different strategies; photoinactivation (PI) by UV-C light and photodynamic inactivation (PDI) by Photodithazine photosensitizer (PDZ). We used two pseudoviral particles harboring the Luciferase-IRES-ZsGreen reporter gene with either a SC2 spike on the membrane or without a spike as a naked control pseudovirus. The mechanism of viral inactivation by UV-C and PDZ-based PDI were studied via biochemical characterizations and quantitative PCR on four levels; free-cell viral damage; viral cell entry; DNA integration; and expression of reporter genes. Both UV-C and PDZ treatments could destroy single stranded RNA (ssRNA) and the spike protein of the virus, with different ratios. However, the virus was still capable of binding and entering into the HEK 293T cells expressing angiotensin-converting enzyme 2 (ACE-2). A dose-dependent manner of UV-C irradiation mostly damages the ssRNA, while PDZ-based PDI mostly destroys the spike and viral membrane in concentration and dose-dependent manners. We observed that the cells infected by the virus and treated with either UV-C or PDZ-based PDI could not express the luciferase reporter gene, signifying the viral inactivation, despite the presence of RNA and DNA intact genes. Full article
(This article belongs to the Special Issue Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications)
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17 pages, 3179 KiB  
Article
Multiple Light-Activated Photodynamic Therapy of Tetraphenylethylene Derivative with AIE Characteristics for Hepatocellular Carcinoma via Dual-Organelles Targeting
by Chuxing Chai, Tao Zhou, Jianfang Zhu, Yong Tang, Jun Xiong, Xiaobo Min, Qi Qin, Min Li, Na Zhao and Chidan Wan
Pharmaceutics 2022, 14(2), 459; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14020459 - 21 Feb 2022
Cited by 9 | Viewed by 2519
Abstract
Photodynamic therapy (PDT) has emerged as a promising locoregional therapy of hepatocellular carcinoma (HCC). The utilization of luminogens with aggregation-induced emission (AIE) characteristics provides a new opportunity to design functional photosensitizers (PS). PSs targeting the critical organelles that are susceptible to reactive oxygen [...] Read more.
Photodynamic therapy (PDT) has emerged as a promising locoregional therapy of hepatocellular carcinoma (HCC). The utilization of luminogens with aggregation-induced emission (AIE) characteristics provides a new opportunity to design functional photosensitizers (PS). PSs targeting the critical organelles that are susceptible to reactive oxygen species damage is a promising strategy to enhance the effectiveness of PDT. In this paper, a new PS, 1-[2-hydroxyethyl]-4-[4-(1,2,2-triphenylvinyl)styryl]pyridinium bromide (TPE-Py-OH) of tetraphenylethylene derivative with AIE feature was designed and synthesized for PDT. The TPE-Py-OH can not only simultaneously target lipid droplets and mitochondria, but also stay in cells for a long period (more than 7 days). Taking advantage of the long retention ability of TPE-Py-OH in tumor, the PDT effect of TPE-Py-OH can be activated through multiple irradiations after one injection, which provides a specific multiple light-activated PDT effect. We believe that this AIE-active PS will be promising for the tracking and photodynamic ablation of HCC with sustained effectiveness. Full article
(This article belongs to the Special Issue Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications)
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13 pages, 59429 KiB  
Article
The In Vivo Quantitative Assessment of the Effectiveness of Low-Dose Photodynamic Therapy on Wound Healing Using Optical Coherence Tomography
by Hala Zuhayri, Viktor V. Nikolaev, Tatiana B. Lepekhina, Ekaterina A. Sandykova, Natalya A. Krivova and Yury V. Kistenev
Pharmaceutics 2022, 14(2), 399; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14020399 - 11 Feb 2022
Cited by 4 | Viewed by 1740
Abstract
The effect of low-dose photodynamic therapy on in vivo wound healing was investigated using optical coherence tomography. This work aims to develop an approach to quantitative assessment of the wound’s state during wound healing including the effect of low-dose photodynamic therapy using topical [...] Read more.
The effect of low-dose photodynamic therapy on in vivo wound healing was investigated using optical coherence tomography. This work aims to develop an approach to quantitative assessment of the wound’s state during wound healing including the effect of low-dose photodynamic therapy using topical application of two different photosensitizers, 5-aminolevulinic acid and methylene blue, and two laser doses of 1 J/cm2 and 4 J/cm2. It was concluded that the laser dose of 4 J/cm2 was better compared to 1 J/cm2 and allowed the wound healing process to accelerate. Full article
(This article belongs to the Special Issue Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications)
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21 pages, 6463 KiB  
Article
Parietin Cyclodextrin-Inclusion Complex as an Effective Formulation for Bacterial Photoinactivation
by Abdallah Mohamed Ayoub, Bernd Gutberlet, Eduard Preis, Ahmed Mohamed Abdelsalam, Alice Abu Dayyih, Ayat Abdelkader, Amir Balash, Jens Schäfer and Udo Bakowsky
Pharmaceutics 2022, 14(2), 357; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14020357 - 04 Feb 2022
Cited by 14 | Viewed by 2428
Abstract
Multidrug resistance in pathogenic bacteria has become a significant public health concern. As an alternative therapeutic option, antimicrobial photodynamic therapy (aPDT) can successfully eradicate antibiotic-resistant bacteria with a lower probability of developing resistance or systemic toxicity commonly associated with the standard antibiotic treatment. [...] Read more.
Multidrug resistance in pathogenic bacteria has become a significant public health concern. As an alternative therapeutic option, antimicrobial photodynamic therapy (aPDT) can successfully eradicate antibiotic-resistant bacteria with a lower probability of developing resistance or systemic toxicity commonly associated with the standard antibiotic treatment. Parietin (PTN), also termed physcion, a natural anthraquinone, is a promising photosensitizer somewhat underrepresented in aPDT because of its poor water solubility and potential to aggregate in the biological environment. This study investigated whether the complexation of PTN with (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD) could increase its solubility, enhance its photophysical properties, and improve its phototoxicity against bacteria. At first, the solubilization behavior and complexation constant of the PTN/HP-β-CD inclusion complexes were evaluated by the phase solubility method. Then, the formation and physicochemical properties of PTN/HP-β-CD complexes were analyzed and confirmed in various ways. At the same time, the photodynamic activity was assessed by the uric acid method. The blue light-mediated photodegradation of PTN in its free and complexed forms were compared. Complexation of PTN increased the aqueous solubility 28-fold and the photostability compared to free PTN. PTN/HP-β-CD complexes reduce the bacterial viability of Staphylococcus saprophyticus and Escherichia coli by > 4.8 log and > 1.0 log after irradiation, respectively. Overall, the low solubility, aggregation potential, and photoinstability of PTN were overcome by its complexation in HP-β-CD, potentially opening up new opportunities for treating infections caused by multidrug-resistant bacteria. Full article
(This article belongs to the Special Issue Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications)
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16 pages, 3935 KiB  
Article
Topical Photodynamic Therapy with Different Forms of 5-Aminolevulinic Acid in the Treatment of Actinic Keratosis
by Joanna Bartosińska, Paulina Szczepanik-Kułak, Dorota Raczkiewicz, Marta Niewiedzioł, Agnieszka Gerkowicz, Dorota Kowalczuk, Mirosław Kwaśny and Dorota Krasowska
Pharmaceutics 2022, 14(2), 346; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14020346 - 01 Feb 2022
Cited by 6 | Viewed by 1866
Abstract
Photodynamic therapy (PDT) is safe and effective in the treatment of patients with actinic keratosis (AK). The aim of the study was to assess the efficacy, tolerability and cosmetic outcome of topical PDT in the treatment of AKs with three forms of photosensitizers: [...] Read more.
Photodynamic therapy (PDT) is safe and effective in the treatment of patients with actinic keratosis (AK). The aim of the study was to assess the efficacy, tolerability and cosmetic outcome of topical PDT in the treatment of AKs with three forms of photosensitizers: 5-Aminolevulinic acid hydrochloride (ALA-HCl), 5-Aminolevulinate methyl ester hydrochloride (MAL-HCl) and 5-Aminolevulinate phosphate (ALA-P). The formulations were applied onto selected scalp/face areas. Fluorescence was assessed with a FotoFinder Dermoscope 800 attachment. Skin areas were irradiated with Red Beam Pro+, Model APRO (MedLight GmbH, Herford, Germany). Applied treatments were assessed during the PDT as well as 7 days and 12 weeks after its completion. Ninety-four percent of patients rated obtained cosmetic effect excellent. The efficacy of applied PSs did not differ significantly. However, pain intensity during the PDT procedure was significantly lower in the area treated with ALA-P (5.8 on average) in comparison to the areas treated with ALA-HCl or MAL-HCl (7.0 on average on 0–10 scale). Obtained results show that ALA-P may undergo more selective accumulation than ALA-HCl and MAL-HCl. Our promising results suggest that PDT with the use of ALA-P in AK treatment may be an advantageous alternative to the already used ALA-HCl and MAL-HCl. Full article
(This article belongs to the Special Issue Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications)
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17 pages, 85265 KiB  
Article
In Vivo Quantification of the Effectiveness of Topical Low-Dose Photodynamic Therapy in Wound Healing Using Two-Photon Microscopy
by Hala Zuhayri, Viktor V. Nikolaev, Anastasia I. Knyazkova, Tatiana B. Lepekhina, Natalya A. Krivova, Valery V. Tuchin and Yury V. Kistenev
Pharmaceutics 2022, 14(2), 287; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14020287 - 26 Jan 2022
Cited by 6 | Viewed by 2954
Abstract
The effect of low-dose photodynamic therapy on in vivo wound healing with topical application of 5-aminolevulinic acid and methylene blue was investigated using an animal model for two laser radiation doses (1 and 4 J/cm2). A second-harmonic-generation-to-auto-fluorescence aging index of the [...] Read more.
The effect of low-dose photodynamic therapy on in vivo wound healing with topical application of 5-aminolevulinic acid and methylene blue was investigated using an animal model for two laser radiation doses (1 and 4 J/cm2). A second-harmonic-generation-to-auto-fluorescence aging index of the dermis (SAAID) was analyzed by two-photon microscopy. SAAID measured at 60–80 μm depths was shown to be a suitable quantitative parameter to monitor wound healing. A comparison of SAAID in healthy and wound tissues during phototherapy showed that both light doses were effective for wound healing; however, healing was better at a dose of 4 J/cm2. Full article
(This article belongs to the Special Issue Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications)
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15 pages, 4510 KiB  
Article
Susceptibility of Dental Caries Microcosm Biofilms to Photodynamic Therapy Mediated by Fotoenticine
by Maíra Terra Garcia, Rafael Araújo da Costa Ward, Nathália Maria Ferreira Gonçalves, Lara Luise Castro Pedroso, José Vieira da Silva Neto, Juliana Ferreira Strixino and Juliana Campos Junqueira
Pharmaceutics 2021, 13(11), 1907; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13111907 - 10 Nov 2021
Cited by 13 | Viewed by 2670
Abstract
Photodynamic therapy (PDT) mediated by Fotoenticine® (FTC), a new photosensitizer derived from chlorin e-6, has shown in vitro inhibitory activity against the cariogenic bacterium Streptococcus mutans. However, its antimicrobial effects must be investigated on biofilm models that represent the microbial complexity [...] Read more.
Photodynamic therapy (PDT) mediated by Fotoenticine® (FTC), a new photosensitizer derived from chlorin e-6, has shown in vitro inhibitory activity against the cariogenic bacterium Streptococcus mutans. However, its antimicrobial effects must be investigated on biofilm models that represent the microbial complexity of caries. Thus, we evaluated the efficacy of FTC-mediated PDT on microcosm biofilms of dental caries. Decayed dentin samples were collected from different patients to form in vitro biofilms. Biofilms were treated with FTC associated with LED irradiation and analyzed by counting the colony forming units (log10 CFU) in selective and non-selective culture media. Furthermore, the biofilm structure and acid production by microorganisms were analyzed using microscopic and spectrophotometric analysis, respectively. The biofilms from different patients showed variations in microbial composition, being formed by streptococci, lactobacilli and yeasts. Altogether, PDT decreased up to 3.7 log10 CFU of total microorganisms, 2.8 log10 CFU of streptococci, 3.2 log10 CFU of lactobacilli and 3.2 log10 CFU of yeasts, and reached eradication of mutans streptococci. PDT was also capable of disaggregating the biofilms and reducing acid concentration in 1.1 to 1.9 mmol lactate/L. It was concluded that FTC was effective in PDT against the heterogeneous biofilms of dental caries. Full article
(This article belongs to the Special Issue Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications)
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16 pages, 2214 KiB  
Article
Effective Treatment against ESBL-Producing Klebsiella pneumoniae through Synergism of the Photodynamic Activity of Re (I) Compounds with Beta-Lactams
by Iván A. González, Annegrett Palavecino, Constanza Núñez, Paulina Dreyse, Felipe Melo-González, Susan M. Bueno and Christian Erick Palavecino
Pharmaceutics 2021, 13(11), 1889; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13111889 - 08 Nov 2021
Cited by 3 | Viewed by 1933
Abstract
Background: Extended-spectrum beta-lactamase (ESBL) and carbapenemase (KPC+) producing Klebsiella pneumoniae are multidrug-resistant bacteria (MDR) with the highest risk to human health. The significant reduction of new antibiotics development can be overcome by complementing with alternative therapies, such as antimicrobial photodynamic therapy [...] Read more.
Background: Extended-spectrum beta-lactamase (ESBL) and carbapenemase (KPC+) producing Klebsiella pneumoniae are multidrug-resistant bacteria (MDR) with the highest risk to human health. The significant reduction of new antibiotics development can be overcome by complementing with alternative therapies, such as antimicrobial photodynamic therapy (aPDI). Through photosensitizer (PS) compounds, aPDI produces local oxidative stress-activated by light (photooxidative stress), nonspecifically killing bacteria. Methodology: Bimetallic Re(I)-based compounds, PSRe-µL1 and PSRe-µL2, were tested in aPDI and compared with a Ru(II)-based PS positive control. The ability of PSRe-µL1 and PSRe-µL2 to inhibit K. pneumoniae was evaluated under a photon flux of 17 µW/cm2. In addition, an improved aPDI effect with imipenem on KPC+ bacteria and a synergistic effect with cefotaxime on ESBL producers of a collection of 118 clinical isolates of K. pneumoniae was determined. Furthermore, trypan blue exclusion assays determined the PS cytotoxicity on mammalian cells. Results: At a minimum dose of 4 µg/mL, both the PSRe-µL1 and PSRe-µL2 significantly inhibited in 3log10 (>99.9%) the bacterial growth and showed a lethality of 60 and 30 min of light exposure, respectively. Furthermore, they were active on clinical isolates of K. pneumoniae at 3–6 log10. Additionally, a remarkably increased effectiveness of aPDI was observed over KPC+ bacteria when mixed with imipenem, and a synergistic effect from 3 to 6log10 over ESBL producers of K. pneumoniae clinic isolates when mixed with cefotaxime was determined for both PSs. Furthermore, the compounds show no dark toxicity and low light-dependent toxicity in vitro to mammalian HEp-2 and HEK293 cells. Conclusion: Compounds PSRe-µL1 and PSRe-µL2 produce an effective and synergistic aPDI effect on KPC+, ESBL, and clinical isolates of K. pneumoniae and have low cytotoxicity in mammalian cells. Full article
(This article belongs to the Special Issue Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications)
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11 pages, 2151 KiB  
Article
Photodynamic Therapy Targeting Macrophages Using IRDye700DX-Liposomes Decreases Experimental Arthritis Development
by Daphne N. Dorst, Marti Boss, Mark Rijpkema, Birgitte Walgreen, Monique M. A. Helsen, Desirée L. Bos, Louis van Bloois, Gerrit Storm, Maarten Brom, Peter Laverman, Peter M. van der Kraan, Mijke Buitinga, Marije I. Koenders and Martin Gotthardt
Pharmaceutics 2021, 13(11), 1868; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13111868 - 05 Nov 2021
Cited by 5 | Viewed by 1912
Abstract
Macrophages play a crucial role in the initiation and progression of rheumatoid arthritis (RA). Liposomes can be used to deliver therapeutics to macrophages by exploiting their phagocytic ability. However, since macrophages serve as the immune system’s first responders, it is inadvisable to systemically [...] Read more.
Macrophages play a crucial role in the initiation and progression of rheumatoid arthritis (RA). Liposomes can be used to deliver therapeutics to macrophages by exploiting their phagocytic ability. However, since macrophages serve as the immune system’s first responders, it is inadvisable to systemically deplete these cells. By loading the liposomes with the photosensitizer IRDye700DX, we have developed and tested a novel way to perform photodynamic therapy (PDT) on macrophages in inflamed joints. PEGylated liposomes were created using the film method and post-inserted with micelles containing IRDye700DX. For radiolabeling, a chelator was also incorporated. RAW 264.7 cells were incubated with liposomes with or without IRDye700DX and exposed to 689 nm light. Viability was determined using CellTiterGlo. Subsequently, biodistribution and PDT studies were performed on mice with collagen-induced arthritis (CIA). PDT using IRDye700DX-loaded liposomes efficiently induced cell death in vitro, whilst no cell death was observed using the control liposomes. Biodistribution of the two compounds in CIA mice was comparable with excellent correlation of the uptake with macroscopic and microscopic arthritis scores. Treatment with 700DX-loaded liposomes significantly delayed arthritis development. Here we have shown the proof-of-principle of performing PDT in arthritic joints using IRDye700DX-loaded liposomes, allowing locoregional treatment of arthritis. Full article
(This article belongs to the Special Issue Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications)
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7 pages, 751 KiB  
Communication
Fluorescence Lifetime Imaging Microscopy of Porphyrins in Helicobacter pylori Biofilms
by Antonella Battisti, Paola Morici and Antonella Sgarbossa
Pharmaceutics 2021, 13(10), 1674; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13101674 - 13 Oct 2021
Cited by 6 | Viewed by 2023
Abstract
Bacterial biofilm constitutes a strong barrier against the penetration of drugs and against the action of the host immune system causing persistent infections hardly treatable by antibiotic therapy. Helicobacter pylori (Hp), the main causative agent for gastritis, peptic ulcer and gastric adenocarcinoma, can [...] Read more.
Bacterial biofilm constitutes a strong barrier against the penetration of drugs and against the action of the host immune system causing persistent infections hardly treatable by antibiotic therapy. Helicobacter pylori (Hp), the main causative agent for gastritis, peptic ulcer and gastric adenocarcinoma, can form a biofilm composed by an exopolysaccharide matrix layer covering the gastric surface where the bacterial cells become resistant and tolerant to the commonly used antibiotics clarithromycin, amoxicillin and metronidazole. Antimicrobial PhotoDynamic Therapy (aPDT) was proposed as an alternative treatment strategy for eradicating bacterial infections, particularly effective for Hp since this microorganism produces and stores up photosensitizing porphyrins. The knowledge of the photophysical characteristics of Hp porphyrins in their physiological biofilm microenvironment is crucial to implement and optimize the photodynamic treatment. Fluorescence lifetime imaging microscopy (FLIM) of intrinsic bacterial porphyrins was performed and data were analyzed by the ‘fit-free’ phasor approach in order to map the distribution of the different fluorescent species within Hp biofilm. Porphyrins inside bacteria were easily distinguished from those dispersed in the matrix suggesting FLIM-phasor technique as a sensitive and rapid tool to monitor the photosensitizer distribution inside bacterial biofilms and to better orientate the phototherapeutic strategy. Full article
(This article belongs to the Special Issue Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications)
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13 pages, 970 KiB  
Article
Application of Photodynamic Therapy with 5-Aminolevulinic Acid to Extracorporeal Photopheresis in the Treatment of Patients with Chronic Graft-versus-Host Disease: A First-in-Human Study
by Eidi Christensen, Olav A. Foss, Petter Quist-Paulsen, Ingrid Staur, Frode Pettersen, Toril Holien, Petras Juzenas and Qian Peng
Pharmaceutics 2021, 13(10), 1558; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13101558 - 26 Sep 2021
Cited by 6 | Viewed by 2732
Abstract
Extracorporeal photopheresis (ECP), an immunomodulatory therapy for the treatment of chronic graft-versus-host disease (cGvHD), exposes isolated white blood cells to photoactivatable 8-methoxypsoralen (8-MOP) and UVA light to induce the apoptosis of T-cells and, hence, to modulate immune responses. However, 8-MOP-ECP kills diseased and [...] Read more.
Extracorporeal photopheresis (ECP), an immunomodulatory therapy for the treatment of chronic graft-versus-host disease (cGvHD), exposes isolated white blood cells to photoactivatable 8-methoxypsoralen (8-MOP) and UVA light to induce the apoptosis of T-cells and, hence, to modulate immune responses. However, 8-MOP-ECP kills diseased and healthy cells with no selectivity and has limited efficacy in many cases. The use of 5-aminolevulinic acid (ALA) and light (ALA-based photodynamic therapy) may be an alternative, as ex vivo investigations show that ALA-ECP kills T-cells from cGvHD patients more selectively and efficiently than those treated with 8-MOP-ECP. The purpose of this phase I-(II) study was to evaluate the safety and tolerability of ALA-ECP in cGvHD patients. The study included 82 treatments in five patients. One patient was discharged due to the progression of the haematological disease. No significant persistent changes in vital signs or laboratory values were detected. In total, 62 adverse events were reported. Two events were severe, 17 were moderate, and 43 were mild symptoms. None of the adverse events evaluated by the internal safety review committee were considered to be likely related to the study medication. The results indicate that ALA-ECP is safe and is mainly tolerated well by cGvHD patients. Full article
(This article belongs to the Special Issue Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications)
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17 pages, 4675 KiB  
Article
Novel Pyropheophorbide Phosphatydic Acids Photosensitizer Combined EGFR siRNA Gene Therapy for Head and Neck Cancer Treatment
by Chia-Hsien Yeh, Juan Chen, Gang Zheng, Leaf Huang and Yih-Chih Hsu
Pharmaceutics 2021, 13(9), 1435; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13091435 - 09 Sep 2021
Cited by 6 | Viewed by 2274
Abstract
This study combined two novel nanomedicines, a novel LCP Pyro PA photodynamic therapy (PDT) and LCP EGFR siRNA gene therapy, to treat head and neck cancer. A novel photosensitizer, pyropheophorbide phosphatydic acids (Pyro PA), was first modified into Lipid-Calcium phosphate nanoparticles named LCP [...] Read more.
This study combined two novel nanomedicines, a novel LCP Pyro PA photodynamic therapy (PDT) and LCP EGFR siRNA gene therapy, to treat head and neck cancer. A novel photosensitizer, pyropheophorbide phosphatydic acids (Pyro PA), was first modified into Lipid-Calcium phosphate nanoparticles named LCP Pyro PA NPs, and targeted with aminoethylanisamide as a novel PDT photosensitizer. EGFR siRNA was encapsulated into LCP NPs to silence EGFR expression. Measured sizes of LCP EGFR siRNA NPs and LCP Pyro-PA NPs were 34.9 ± 3.0 and 20 nm respectively, and their zeta potentials were 51.8 ± 1.8 and 52.0 ± 7.6 mV respectively. In vitro studies showed that EGFR siRNA was effectively knocked down after photodynamic therapy (PDT) with significant inhibition of cancer growth. SCC4 or SAS xenografted nude mice were used to verify therapeutic efficacy. The LCP Control siRNA+PDT group of SCC4 and SAS showed significantly reduced tumor volume compared to the phosphate buffered saline (PBS) group. In the LCP-EGFR siRNA+LCP Pyro PA without light group and LCP EGFR siRNA + PBS with light group, SCC4 and SAS tumor volumes were reduced by ~140% and ~150%, respectively, compared to the PBS group. The LCP EGFR siRNA+PDT group of SCC4 and SAS tumor volumes were reduced by ~205% and ~220%, respectively, compared to the PBS group. Combined therapy showed significant tumor volume reduction compared to PBS, control siRNA, or PDT alone. QPCR results showed EGFR expression was significantly reduced after treatment with EGFR siRNA with PDT in SCC4 and SAS compared to control siRNA or PDT alone. Western blot results confirmed decreased EGFR protein expression in the combined therapy group. No toxic results were found in serum biomarkers. No inflammatory factors were found in heart, liver and kidney tissues. Results suggest that the novel LCP Pyro PA mediated PDT combined with LCP siEGFR NPs could be developed in clinical modalities for treating human head and neck cancer in the future. Full article
(This article belongs to the Special Issue Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications)
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15 pages, 5266 KiB  
Article
Hypericin and Pheophorbide a Mediated Photodynamic Therapy Fighting MRSA Wound Infections: A Translational Study from In Vitro to In Vivo
by Ben Chung Lap Chan, Priyanga Dharmaratne, Baiyan Wang, Kit Man Lau, Ching Ching Lee, David Wing Shing Cheung, Judy Yuet Wa Chan, Grace Gar Lee Yue, Clara Bik San Lau, Chun Kwok Wong, Kwok Pui Fung and Margaret Ip
Pharmaceutics 2021, 13(9), 1399; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13091399 - 03 Sep 2021
Cited by 17 | Viewed by 2953
Abstract
High prevalence rates of methicillin-resistant Staphylococcus aureus (MRSA) and lack of effective antibacterial treatments urge discovery of alternative therapeutic modalities. The advent of antibacterial photodynamic therapy (aPDT) is a promising alternative, composing rapid, nonselective cell destruction without generating resistance. We used a panel [...] Read more.
High prevalence rates of methicillin-resistant Staphylococcus aureus (MRSA) and lack of effective antibacterial treatments urge discovery of alternative therapeutic modalities. The advent of antibacterial photodynamic therapy (aPDT) is a promising alternative, composing rapid, nonselective cell destruction without generating resistance. We used a panel of clinically relevant MRSA to evaluate hypericin (Hy) and pheophobide a (Pa)-mediated PDT with clinically approved methylene blue (MB). We translated the promising in vitro anti-MRSA activity of selected compounds to a full-thick MRSA wound infection model in mice (in vivo) and the interaction of aPDT innate immune system (cytotoxicity towards neutrophils). Hy-PDT consistently displayed lower minimum bactericidal concentration (MBC) values (0.625–10 µM) against ATCC RN4220/pUL5054 and a whole panel of community-associated (CA)-MRSA compared to Pa or MB. Interestingly, Pa-PDT and Hy-PDT topical application demonstrated encouraging in vivo anti-MRSA activity (>1 log10 CFU reduction). Furthermore, histological analysis showed wound healing via re-epithelization was best in the Hy-PDT group. Importantly, the dark toxicity of Hy was significantly lower (p < 0.05) on neutrophils compared to Pa or MB. Overall, Hy-mediated PDT is a promising alternative to treat MRSA wound infections, and further rigorous mechanistic studies are warranted. Full article
(This article belongs to the Special Issue Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications)
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22 pages, 3772 KiB  
Article
Improvement of Pulmonary Photodynamic Therapy: Nebulisation of Curcumin-Loaded Tetraether Liposomes
by Jennifer Lehmann, Michael R. Agel, Konrad H. Engelhardt, Shashank R. Pinnapireddy, Sabine Agel, Lili Duse, Eduard Preis, Matthias Wojcik and Udo Bakowsky
Pharmaceutics 2021, 13(8), 1243; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13081243 - 12 Aug 2021
Cited by 16 | Viewed by 2694
Abstract
Lung cancer is one of the most common causes for a high number of cancer related mortalities worldwide. Therefore, it is important to improve the therapy by finding new targets and developing convenient therapies. One of these novel non-invasive strategies is the combination [...] Read more.
Lung cancer is one of the most common causes for a high number of cancer related mortalities worldwide. Therefore, it is important to improve the therapy by finding new targets and developing convenient therapies. One of these novel non-invasive strategies is the combination of pulmonary delivered tetraether liposomes and photodynamic therapy. In this study, liposomal model formulations containing the photosensitiser curcumin were nebulised via two different technologies, vibrating-mesh nebulisation and air-jet nebulisation, and compared with each other. Particle size and ζ-potential of the liposomes were investigated using dynamic light scattering and laser Doppler anemometry, respectively. Furthermore, atomic force microscopy and transmission electron microscopy were used to determine the morphological characteristics. Using a twin glass impinger, suitable aerodynamic properties were observed, with the fine particle fraction of the aerosols being ≤62.7 ± 1.6%. In vitro irradiation experiments on lung carcinoma cells (A549) revealed an excellent cytotoxic response of the nebulised liposomes in which the stabilisation of the lipid bilayer was the determining factor. Internalisation of nebulised curcumin-loaded liposomes was visualised utilising confocal laser scanning microscopy. Based on these results, the pulmonary application of curcumin-loaded tetraether liposomes can be considered as a promising approach for the photodynamic therapy against lung cancer. Full article
(This article belongs to the Special Issue Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications)
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13 pages, 516 KiB  
Article
In Vitro Effect of Photodynamic Therapy with Different Lights and Combined or Uncombined with Chlorhexidine on Candida spp.
by Vanesa Pérez-Laguna, Yolanda Barrena-López, Yolanda Gilaberte and Antonio Rezusta
Pharmaceutics 2021, 13(8), 1176; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13081176 - 30 Jul 2021
Cited by 9 | Viewed by 1845
Abstract
Candidiasis is very common and complicated to treat in some cases due to increased resistance to antifungals. Antimicrobial photodynamic therapy (aPDT) is a promising alternative treatment. It is based on the principle that light of a specific wavelength activates a photosensitizer molecule resulting [...] Read more.
Candidiasis is very common and complicated to treat in some cases due to increased resistance to antifungals. Antimicrobial photodynamic therapy (aPDT) is a promising alternative treatment. It is based on the principle that light of a specific wavelength activates a photosensitizer molecule resulting in the generation of reactive oxygen species that are able to kill pathogens. The aim here is the in vitro photoinactivation of three strains of Candida spp., Candida albicans ATCC 10231, Candida parapsilosis ATCC 22019 and Candida krusei ATCC 6258, using aPDT with different sources of irradiation and the photosensitizer methylene blue (MB), alone or in combination with chlorhexidine (CHX). Irradiation was carried out at a fluence of 18 J/cm2 with a light-emitting diode (LED) lamp emitting in red (625 nm) or a white metal halide lamp (WMH) that emits at broad-spectrum white light (420–700 nm). After the photodynamic treatment, the antimicrobial effect is evaluated by counting colony forming units (CFU). MB-aPDT produces a 6 log10 reduction in the number of CFU/100 μL of Candida spp., and the combination with CHX enhances the effect of photoinactivation (effect achieved with lower concentration of MB). Both lamps have similar efficiencies, but the WMH lamp is slightly more efficient. This work opens the doors to a possible clinical application of the combination for resistant or persistent forms of Candida infections. Full article
(This article belongs to the Special Issue Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications)
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25 pages, 8679 KiB  
Article
Insight into the Web of Stress Responses Triggered at Gene Expression Level by Porphyrin-PDT in HT29 Human Colon Carcinoma Cells
by Maria Dobre, Rica Boscencu, Ionela Victoria Neagoe, Mihaela Surcel, Elena Milanesi and Gina Manda
Pharmaceutics 2021, 13(7), 1032; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13071032 - 07 Jul 2021
Cited by 8 | Viewed by 2210
Abstract
Photodynamic therapy (PDT), a highly targeted therapy with acceptable side effects, has emerged as a promising therapeutic option in oncologic pathology. One of the issues that needs to be addressed is related to the complex network of cellular responses developed by tumor cells [...] Read more.
Photodynamic therapy (PDT), a highly targeted therapy with acceptable side effects, has emerged as a promising therapeutic option in oncologic pathology. One of the issues that needs to be addressed is related to the complex network of cellular responses developed by tumor cells in response to PDT. In this context, this study aims to characterize in vitro the stressors and the corresponding cellular responses triggered by PDT in the human colon carcinoma HT29 cell line, using a new asymmetric porphyrin derivative (P2.2) as a photosensitizer. Besides investigating the ability of P2.2-PDT to reduce the number of viable tumor cells at various P2.2 concentrations and fluences of the activating light, we assessed, using qRT-PCR, the expression levels of 84 genes critically involved in the stress response of PDT-treated cells. Results showed a fluence-dependent decrease of viable tumor cells at 24 h post-PDT, with few cells that seem to escape from PDT. We highlighted following P2.2-PDT the concomitant activation of particular cellular responses to oxidative stress, hypoxia, DNA damage and unfolded protein responses and inflammation. A web of inter-connected stressors was induced by P2.2-PDT, which underlies cell death but also elicits protective mechanisms that may delay tumor cell death or even defend these cells against the deleterious effects of PDT. Full article
(This article belongs to the Special Issue Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications)
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17 pages, 1955 KiB  
Article
Effective Photodynamic Therapy with Ir(III) for Virulent Clinical Isolates of Extended-Spectrum Beta-Lactamase Klebsiella pneumoniae
by Constanza Núñez, Annegrett Palavecino, Iván A. González, Paulina Dreyse and Christian Erick Palavecino
Pharmaceutics 2021, 13(5), 603; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13050603 - 22 Apr 2021
Cited by 5 | Viewed by 2100
Abstract
Background: The extended-spectrum beta-lactamase (ESBL) Klebsiella pneumoniae is one of the leading causes of health-associated infections (HAIs), whose antibiotic treatments have been severely reduced. Moreover, HAI bacteria may harbor pathogenic factors such as siderophores, enzymes, or capsules, which increase the virulence of these [...] Read more.
Background: The extended-spectrum beta-lactamase (ESBL) Klebsiella pneumoniae is one of the leading causes of health-associated infections (HAIs), whose antibiotic treatments have been severely reduced. Moreover, HAI bacteria may harbor pathogenic factors such as siderophores, enzymes, or capsules, which increase the virulence of these strains. Thus, new therapies, such as antimicrobial photodynamic inactivation (aPDI), are needed. Method: A collection of 118 clinical isolates of K. pneumoniae was characterized by susceptibility and virulence through the determination of the minimum inhibitory concentration (MIC) of amikacin (Amk), cefotaxime (Cfx), ceftazidime (Cfz), imipenem (Imp), meropenem (Mer), and piperacillin–tazobactam (Pip–Taz); and, by PCR, the frequency of the virulence genes K2, magA, rmpA, entB, ybtS, and allS. Susceptibility to innate immunity, such as human serum, macrophages, and polymorphonuclear cells, was tested. All the strains were tested for sensitivity to the photosensitizer PSIR-3 (4 µg/mL) in a 17 µW/cm2 for 30 min aPDI. Results: A significantly higher frequency of virulence genes in ESBL than non-ESBL bacteria was observed. The isolates of the genotype K2+, ybtS+, and allS+ display enhanced virulence, since they showed higher resistance to human serum, as well as to phagocytosis. All strains are susceptible to the aPDI with PSIR-3 decreasing viability in 3log10. The combined treatment with Cfx improved the aPDI to 6log10 for the ESBL strains. The combined treatment is synergistic, as it showed a fractional inhibitory concentration (FIC) index value of 0.15. Conclusions: The aPDI effectively inhibits clinical isolates of K. pneumoniae, including the riskier strains of ESBL-producing bacteria and the K2+, ybtS+, and allS+ genotype. The aPDI with PSIR-3 is synergistic with Cfx. Full article
(This article belongs to the Special Issue Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications)
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Review

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17 pages, 1004 KiB  
Review
Combination-Based Strategies for the Treatment of Actinic Keratoses with Photodynamic Therapy: An Evidence-Based Review
by Stefano Piaserico, Roberto Mazzetto, Emma Sartor and Carlotta Bortoletti
Pharmaceutics 2022, 14(8), 1726; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14081726 - 18 Aug 2022
Cited by 7 | Viewed by 2216
Abstract
Photodynamic therapy (PDT) is a highly effective and widely adopted treatment strategy for many skin diseases, particularly for multiple actinic keratoses (AKs). However, PDT is ineffective in some cases, especially if AKs occur in the acral part of the body. Several methods to [...] Read more.
Photodynamic therapy (PDT) is a highly effective and widely adopted treatment strategy for many skin diseases, particularly for multiple actinic keratoses (AKs). However, PDT is ineffective in some cases, especially if AKs occur in the acral part of the body. Several methods to improve the efficacy of PDT without significantly increasing the risks of side effects have been proposed. In this study, we reviewed the combination-based PDT treatments described in the literature for treating AKs; both post-treatment and pretreatment were considered including topical (i.e., diclofenac, imiquimod, adapalene, 5-fluorouracil, and calcitriol), systemic (i.e., acitretin, methotrexate, and polypodium leucotomos), and mechanical–physical (i.e., radiofrequency, thermomechanical fractional injury, microneedling, microdermabrasion, and laser) treatment strategies. Topical pretreatments with imiquimod, adapalene, 5-fluorouracil, and calcipotriol were more successful than PDT alone in treating AKs, while the effect of diclofenac gel was less clear. Both mechanical laser treatment with CO2 and Er:YAG (Erbium:Yttrium–Aluminum–Garnet) as well as systemic treatment with Polypodium leucotomos were also effective. Different approaches were relatively more effective in particular situations such as in immunosuppressed patients, AKs in the extremities, or thicker AKs. Conclusions: Several studies showed that a combination-based approach enhanced the effectiveness of PDT. However, more studies are needed to further understand the effectiveness of combination therapy in clinical practice and to investigate the role of acitretin, methotrexate, vitamin D, thermomechanical fractional injury, and microdermabrasion in humans. Full article
(This article belongs to the Special Issue Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications)
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56 pages, 1841 KiB  
Review
Antimicrobial Photodynamic Therapy: Latest Developments with a Focus on Combinatory Strategies
by Raphaëlle Youf, Max Müller, Ali Balasini, Franck Thétiot, Mareike Müller, Alizé Hascoët, Ulrich Jonas, Holger Schönherr, Gilles Lemercier, Tristan Montier and Tony Le Gall
Pharmaceutics 2021, 13(12), 1995; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13121995 - 24 Nov 2021
Cited by 63 | Viewed by 7765
Abstract
Antimicrobial photodynamic therapy (aPDT) has become a fundamental tool in modern therapeutics, notably due to the expanding versatility of photosensitizers (PSs) and the numerous possibilities to combine aPDT with other antimicrobial treatments to combat localized infections. After revisiting the basic principles of aPDT, [...] Read more.
Antimicrobial photodynamic therapy (aPDT) has become a fundamental tool in modern therapeutics, notably due to the expanding versatility of photosensitizers (PSs) and the numerous possibilities to combine aPDT with other antimicrobial treatments to combat localized infections. After revisiting the basic principles of aPDT, this review first highlights the current state of the art of curative or preventive aPDT applications with relevant clinical trials. In addition, the most recent developments in photochemistry and photophysics as well as advanced carrier systems in the context of aPDT are provided, with a focus on the latest generations of efficient and versatile PSs and the progress towards hybrid-multicomponent systems. In particular, deeper insight into combinatory aPDT approaches is afforded, involving non-radiative or other light-based modalities. Selected aPDT perspectives are outlined, pointing out new strategies to target and treat microorganisms. Finally, the review works out the evolution of the conceptually simple PDT methodology towards a much more sophisticated, integrated, and innovative technology as an important element of potent antimicrobial strategies. Full article
(This article belongs to the Special Issue Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications)
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35 pages, 1691 KiB  
Review
Latest Innovations and Nanotechnologies with Curcumin as a Nature-Inspired Photosensitizer Applied in the Photodynamic Therapy of Cancer
by Laura Marinela Ailioaie, Constantin Ailioaie and Gerhard Litscher
Pharmaceutics 2021, 13(10), 1562; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13101562 - 26 Sep 2021
Cited by 26 | Viewed by 4517
Abstract
In the context of the high incidence of cancer worldwide, state-of-the-art photodynamic therapy (PDT) has entered as a usual protocol of attempting to eradicate cancer as a minimally invasive procedure, along with pharmacological resources and radiation therapy. The photosensitizer (PS) excited at certain [...] Read more.
In the context of the high incidence of cancer worldwide, state-of-the-art photodynamic therapy (PDT) has entered as a usual protocol of attempting to eradicate cancer as a minimally invasive procedure, along with pharmacological resources and radiation therapy. The photosensitizer (PS) excited at certain wavelengths of the applied light source, in the presence of oxygen releases several free radicals and various oxidation products with high cytotoxic potential, which will lead to cell death in irradiated cancerous tissues. Current research focuses on the potential of natural products as a superior generation of photosensitizers, which through the latest nanotechnologies target tumors better, are less toxic to neighboring tissues, but at the same time, have improved light absorption for the more aggressive and widespread forms of cancer. Curcumin incorporated into nanotechnologies has a higher intracellular absorption, a higher targeting rate, increased toxicity to tumor cells, accelerates the activity of caspases and DNA cleavage, decreases the mitochondrial activity of cancer cells, decreases their viability and proliferation, decreases angiogenesis, and finally induces apoptosis. It reduces the size of the primary tumor, reverses multidrug resistance in chemotherapy and decreases resistance to radiation therapy in neoplasms. Current research has shown that the use of PDT and nanoformulations of curcumin has a modulating effect on ROS generation, so light or laser irradiation will lead to excessive ROS growth, while nanocurcumin will reduce the activation of ROS-producing enzymes or will determine the quick removal of ROS, seemingly opposite but synergistic phenomena by inducing neoplasm apoptosis, but at the same time, accelerating the repair of nearby tissue. The latest curcumin nanoformulations have a huge potential to optimize PDT, to overcome major side effects, resistance to chemotherapy, relapses and metastases. All the studies reviewed and presented revealed great potential for the applicability of nanoformulations of curcumin and PDT in cancer therapy. Full article
(This article belongs to the Special Issue Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications)
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17 pages, 24243 KiB  
Review
Liposome Photosensitizer Formulations for Effective Cancer Photodynamic Therapy
by Sherif Ashraf Fahmy, Hassan Mohamed El-Said Azzazy and Jens Schaefer
Pharmaceutics 2021, 13(9), 1345; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13091345 - 27 Aug 2021
Cited by 30 | Viewed by 4047
Abstract
Photodynamic therapy (PDT) is a promising non-invasive strategy in the fight against that which circumvents the systemic toxic effects of chemotherapeutics. It relies on photosensitizers (PSs), which are photoactivated by light irradiation and interaction with molecular oxygen. This generates highly reactive oxygen species [...] Read more.
Photodynamic therapy (PDT) is a promising non-invasive strategy in the fight against that which circumvents the systemic toxic effects of chemotherapeutics. It relies on photosensitizers (PSs), which are photoactivated by light irradiation and interaction with molecular oxygen. This generates highly reactive oxygen species (such as 1O2, H2O2, O2, ·OH), which kill cancer cells by necrosis or apoptosis. Despite the promising effects of PDT in cancer treatment, it still suffers from several shortcomings, such as poor biodistribution of hydrophobic PSs, low cellular uptake, and low efficacy in treating bulky or deep tumors. Hence, various nanoplatforms have been developed to increase PDT treatment effectiveness and minimize off-target adverse effects. Liposomes showed great potential in accommodating different PSs, chemotherapeutic drugs, and other therapeutically active molecules. Here, we review the state-of-the-art in encapsulating PSs alone or combined with other chemotherapeutic drugs into liposomes for effective tumor PDT. Full article
(This article belongs to the Special Issue Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications)
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16 pages, 2302 KiB  
Review
Photodynamic Therapy Review: Principles, Photosensitizers, Applications, and Future Directions
by José H. Correia, José A. Rodrigues, Sara Pimenta, Tao Dong and Zhaochu Yang
Pharmaceutics 2021, 13(9), 1332; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13091332 - 25 Aug 2021
Cited by 335 | Viewed by 16806
Abstract
Photodynamic therapy (PDT) is a minimally invasive therapeutic modality that has gained great attention in the past years as a new therapy for cancer treatment. PDT uses photosensitizers that, after being excited by light at a specific wavelength, react with the molecular oxygen [...] Read more.
Photodynamic therapy (PDT) is a minimally invasive therapeutic modality that has gained great attention in the past years as a new therapy for cancer treatment. PDT uses photosensitizers that, after being excited by light at a specific wavelength, react with the molecular oxygen to create reactive oxygen species in the target tissue, resulting in cell death. Compared to conventional therapeutic modalities, PDT presents greater selectivity against tumor cells, due to the use of photosensitizers that are preferably localized in tumor lesions, and the precise light irradiation of these lesions. This paper presents a review of the principles, mechanisms, photosensitizers, and current applications of PDT. Moreover, the future path on the research of new photosensitizers with enhanced tumor selectivity, featuring the improvement of PDT effectiveness, has also been addressed. Finally, new applications of PDT have been covered. Full article
(This article belongs to the Special Issue Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications)
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42 pages, 6715 KiB  
Review
Effectiveness of Antimicrobial Photodynamic Therapy in the Treatment of Periodontitis: A Systematic Review and Meta-Analysis of In Vivo Human Randomized Controlled Clinical Trials
by Snehal Dalvi, Stefano Benedicenti, Tudor Sălăgean, Ioana Roxana Bordea and Reem Hanna
Pharmaceutics 2021, 13(6), 836; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13060836 - 04 Jun 2021
Cited by 19 | Viewed by 3506
Abstract
This systematic review and meta-analysis evaluated antimicrobial photodynamic therapy (aPDT) efficacy in periodontitis. The review protocol was conducted in accordance with PRISMA statements, Cochrane Collaboration recommendations and is registered in PROSPERO (CRD 42020161516). Electronic and hand search strategies were undertaken to gather data [...] Read more.
This systematic review and meta-analysis evaluated antimicrobial photodynamic therapy (aPDT) efficacy in periodontitis. The review protocol was conducted in accordance with PRISMA statements, Cochrane Collaboration recommendations and is registered in PROSPERO (CRD 42020161516). Electronic and hand search strategies were undertaken to gather data on in vivo human RCTs followed by qualitative analysis. Differences in probing pocket depth (PPD) and clinical attachment level (CAL) were calculated with 95% confidence intervals and pooled in random effects model at three and six months. Heterogeneity was analyzed, using Q and I2 tests. Publication bias was assessed by visual examination of the funnel plot symmetry. Sixty percent of 31 eligible studies showed a high risk of bias. Meta-analysis on 18 studies showed no additional benefit in split mouth studies in terms of PPD reduction (SMD 0.166; 95% CI −0.278 to 0.611; P = 0.463) and CAL gain (SMD 0.092; 95% CI −0.013 to 0.198; P = 0.088). Similar findings noted for parallel group studies; PPD reduction (SMD 0.076; 95% CI −0.420 to 0.573; P = 0.763) and CAL gain (SMD 0.056; 95% CI −0.408 to 0.552; P = 0.745). Sensitivity analysis minimized heterogeneity for both outcome variables; however, intergroup differences were not statistically significant. Future research should aim for well-designed RCTs in order to determine the effectiveness of aPDT. Full article
(This article belongs to the Special Issue Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications)
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17 pages, 990 KiB  
Review
Potential of Cyanine Derived Dyes in Photodynamic Therapy
by Natalia Lange, Wojciech Szlasa, Jolanta Saczko and Agnieszka Chwiłkowska
Pharmaceutics 2021, 13(6), 818; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13060818 - 31 May 2021
Cited by 63 | Viewed by 5199
Abstract
Photodynamic therapy (PDT) is a method of cancer treatment that leads to the disintegration of cancer cells and has developed significantly in recent years. The clinically used photosensitizers are primarily porphyrin, which absorbs light in the red spectrum and their absorbance maxima are [...] Read more.
Photodynamic therapy (PDT) is a method of cancer treatment that leads to the disintegration of cancer cells and has developed significantly in recent years. The clinically used photosensitizers are primarily porphyrin, which absorbs light in the red spectrum and their absorbance maxima are relatively short. This review presents group of compounds and their derivatives that are considered to be potential photosensitizers in PDT. Cyanine dyes are compounds that typically absorb light in the visible to near-infrared-I (NIR-I) spectrum range (750–900 nm). This meta-analysis comprises the current studies on cyanine dye derivatives, such as indocyanine green (so far used solely as a diagnostic agent), heptamethine and pentamethine dyes, squaraine dyes, merocyanines and phthalocyanines. The wide array of the cyanine derivatives arises from their structural modifications (e.g., halogenation, incorporation of metal atoms or organic structures, or synthesis of lactosomes, emulsions or conjugation). All the following modifications aim to increase solubility in aqueous media, enhance phototoxicity, and decrease photobleaching. In addition, the changes introduce new features like pH-sensitivity. The cyanine dyes involved in photodynamic reactions could be incorporated into sets of PDT agents. Full article
(This article belongs to the Special Issue Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications)
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