Pharmaceutics

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3 pages, 396 KiB

Open AccessEditorial

Photodynamic Therapy: A Rising Star in Pharmaceutical Applications

by Eduard Preis and Udo Bakowsky

Pharmaceutics 2024, 16(8), 1072; https://doi.org/10.3390/pharmaceutics16081072 - 16 Aug 2024

Viewed by 656

Abstract

The interest in photodynamic therapy (PDT) has increased remarkably over the past years, with over 75% of all related articles published after 2010 (Figure 1) [...] Full article

(This article belongs to the Special Issue Photodynamic Therapy: Rising Star in Pharmaceutical Applications)

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Research

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12 pages, 1837 KiB

Open AccessArticle

Application of Photodynamic Therapy with 5-Aminolevulinic Acid to Extracorporeal Photopheresis in the Treatment of Cutaneous T-Cell Lymphoma: A First-in-Human Phase I/II Study

by Eidi Christensen, Olav Andreas Foss, Toril Holien, Petras Juzenas and Qian Peng

Pharmaceutics 2024, 16(6), 815; https://doi.org/10.3390/pharmaceutics16060815 - 16 Jun 2024

Cited by 1 | Viewed by 1111

Abstract

Extracorporeal photopheresis (ECP) is a therapeutic modality used for T-cell-mediated disorders. This approach involves exposing isolated white blood cells to photoactivatable 8-methoxypsoralen (8-MOP) and UVA light, aiming to induce apoptosis in T-cells and thereby modulate immune responses. However, conventional 8-MOP-ECP lacks cell selectivity, [...] Read more.

Extracorporeal photopheresis (ECP) is a therapeutic modality used for T-cell-mediated disorders. This approach involves exposing isolated white blood cells to photoactivatable 8-methoxypsoralen (8-MOP) and UVA light, aiming to induce apoptosis in T-cells and thereby modulate immune responses. However, conventional 8-MOP-ECP lacks cell selectivity, killing both healthy and diseased cells, and has shown limited treatment efficacy. An alternative approach under investigation involves the use of 5-aminolevulinic acid (ALA) in conjunction with light, referred to as ALA-based photodynamic therapy. Our previous ex vivo studies suggest that ALA-ECP exhibits greater selectivity and efficiency in killing T-cells derived from patients with T-cell-mediated disorders compared to those treated with 8-MOP-ECP. We have conducted a clinical phase I–(II) study evaluating ALA-ECP safety and tolerability in cutaneous T-cell lymphoma (CTCL). Here, 20 ALA-ECP treatments were administered to one CTCL patient, revealing no significant changes in vital signs. Two adverse events were reported; both evaluated by the Internal Safety Review Committee as non-serious. In addition, five conceivable events with mainly mild symptoms took place. During the study period, a 53% reduction in skin involvement and a 50% reduction in pruritus was observed. In conclusion, the results indicate that ALA-ECP treatment is safe and well tolerated. Full article

(This article belongs to the Special Issue Photodynamic Therapy: Rising Star in Pharmaceutical Applications)

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23 pages, 4265 KiB

Open AccessArticle

Photodynamic Eradication of Pseudomonas aeruginosa with Ru-Photosensitizers Encapsulated in Enzyme Degradable Nanocarriers

by Kawaljit Kaur, Max Müller, Mareike Müller and Holger Schönherr

Pharmaceutics 2023, 15(12), 2683; https://doi.org/10.3390/pharmaceutics15122683 - 27 Nov 2023

Cited by 2 | Viewed by 1358

Abstract

The development of new approaches for the treatment of the increasingly antibiotic-resistant pathogen Pseudomonas aeruginosa was targeted by enhancing the effect of local antimicrobial photodynamic therapy (aPDT) using poly(ethylene glycol)-block-poly(lactic acid) (PEG₁₁₄-block-PLA_x) nanocarriers that were [...] Read more.

The development of new approaches for the treatment of the increasingly antibiotic-resistant pathogen Pseudomonas aeruginosa was targeted by enhancing the effect of local antimicrobial photodynamic therapy (aPDT) using poly(ethylene glycol)-block-poly(lactic acid) (PEG₁₁₄-block-PLA_x) nanocarriers that were loaded with a ruthenium-based photosensitizer (PS). The action of tris(1,10-phenanthroline) ruthenium (II) bis(hexafluorophosphate) (RuPhen3) encapsulated in PEG₁₁₄-block-PLA_x micelles and vesicles was shown to result in an appreciable aPDT inactivation efficiency against planktonic Pseudomonas aeruginosa. In particular, the encapsulation of the PS, its release, and the efficiency of singlet oxygen (¹O₂) generation upon irradiation with blue light were studied spectroscopically. The antimicrobial effect was analyzed with two strains of Pseudomonas aeruginosa. Compared with PS-loaded micelles, formulations of the PS-loaded vesicles showed 10 times enhanced activity with a strong photodynamic inactivation effect of at least a 4.7 log reduction against both a Pseudomonas aeruginosa lab strain and a clinical isolate collected from the lung of a cystic fibrosis (CF) patient. This work lays the foundation for the targeted eradication of Pseudomonas aeruginosa using aPDT in various medical application areas. Full article

(This article belongs to the Special Issue Photodynamic Therapy: Rising Star in Pharmaceutical Applications)

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14 pages, 2721 KiB

Open AccessArticle

Novel Iron-Chelating Prodrug Significantly Enhanced Fluorescence-Mediated Detection of Glioma Cells Experimentally In Vitro

by Charlotte Reburn, George Gawthorpe, Alexis Perry, Mark Wood and Alison Curnow

Pharmaceutics 2023, 15(12), 2668; https://doi.org/10.3390/pharmaceutics15122668 - 24 Nov 2023

Cited by 1 | Viewed by 1055

Abstract

(1) Background: The protoporphyrin IX (PpIX)-mediated fluorescence-guided resection and interoperative photodynamic therapy (PDT) of remaining cells may be effective adjuvants to the resection of glioma. Both processes may be enhanced by increasing intracellular PpIX concentrations, which can be achieved through iron chelation. AP2-18 [...] Read more.

(1) Background: The protoporphyrin IX (PpIX)-mediated fluorescence-guided resection and interoperative photodynamic therapy (PDT) of remaining cells may be effective adjuvants to the resection of glioma. Both processes may be enhanced by increasing intracellular PpIX concentrations, which can be achieved through iron chelation. AP2-18 is a novel combinational drug, which ester-links a PpIX precursor (aminolaevulinic acid; ALA) to an iron-chelating agent (CP94). (2) Methods: Human glioma U-87 MG cells were cultured in 96-well plates for 24 h and incubated for 3 or 6 h with various test compound combinations: ALA (±) CP94, methyl aminolevulinate (MAL) (±) CP94 and AP2-18. PpIX fluorescence was measured at 0, 3 or 6 h with a Bio-tek Synergy HT plate reader, as well as immediately after irradiation with a 635 nm red light (Aktilite CL16 LED array), representing the PDT procedure. Cell viability post-irradiation was assessed using the neutral red assay. (3) Results: AP2-18 significantly increased PpIX fluorescence compared to all other test compounds. All treatment protocols effectively achieved PDT-induced cytotoxicity, with no significant difference between test compound combinations. (4) Conclusions: AP2-18 has potential to improve the efficacy of fluorescence-guided resection either with or without the subsequent intraoperative PDT of glioma. Future work should feature a more complex in vitro model of the glioma microenvironment. Full article

(This article belongs to the Special Issue Photodynamic Therapy: Rising Star in Pharmaceutical Applications)

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17 pages, 12498 KiB

Open AccessEditor’s ChoiceArticle

Lipid-Coated Polymeric Nanoparticles for the Photodynamic Therapy of Head and Neck Squamous Cell Carcinomas

by Valeri Roschenko, Abdallah M. Ayoub, Konrad Engelhardt, Jens Schäfer, Muhammad Umair Amin, Eduard Preis, Robert Mandic and Udo Bakowsky

Pharmaceutics 2023, 15(10), 2412; https://doi.org/10.3390/pharmaceutics15102412 - 2 Oct 2023

Cited by 5 | Viewed by 1607

Abstract

Next to alcohol and tobacco abuse, infection with human papillomaviruses (HPVs) is a major risk factor for developing head and neck squamous cell carcinomas (HNSCCs), leading to 350,000 casualties worldwide each year. Limited therapy options and drug resistance raise the urge for alternative [...] Read more.

Next to alcohol and tobacco abuse, infection with human papillomaviruses (HPVs) is a major risk factor for developing head and neck squamous cell carcinomas (HNSCCs), leading to 350,000 casualties worldwide each year. Limited therapy options and drug resistance raise the urge for alternative methods such as photodynamic therapy (PDT), a minimally invasive procedure used to treat HNSCC and other cancers. We prepared lipid-coated polymeric nanoparticles encapsulating curcumin as the photosensitizer (CUR-LCNPs). The prepared CUR-LCNPs were in the nanometer range (153.37 ± 1.58 nm) and showed an encapsulation efficiency of 92.69 ± 0.03%. Proper lipid coating was visualized using atomic force microscopy (AFM). The CUR-LCNPs were tested in three HPV^pos and three HPV^neg HNSCC lines regarding their uptake capabilities and in vitro cell killing capacity, revealing a variable but highly significant tumor cell inhibiting effect in all tested HNSCC cell lines. No significant differences were detected between the HPV^pos and HPV^neg HNSCC groups (mean IC₅₀: (9.34 ± 4.73 µmol/L vs. 6.88 ± 1.03 µmol/L), suggesting CUR-LCNPs/PDT to be a promising therapeutic option for HNSCC patients independent of their HPV status. Full article

(This article belongs to the Special Issue Photodynamic Therapy: Rising Star in Pharmaceutical Applications)

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Review

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18 pages, 3524 KiB

Open AccessEditor’s ChoiceReview

Innovative Phosphorene Nanoplatform for Light Antimicrobial Therapy

by Elisa Passaglia and Antonella Sgarbossa

Pharmaceutics 2023, 15(12), 2748; https://doi.org/10.3390/pharmaceutics15122748 - 9 Dec 2023

Cited by 1 | Viewed by 2476

Abstract

Over the past few years, antibiotic resistance has reached global dimensions as a major threat to public health. Consequently, there is a pressing need to find effective alternative therapies and therapeutic agents to combat drug-resistant pathogens. Photodynamic therapy (PDT), largely employed as a [...] Read more.

Over the past few years, antibiotic resistance has reached global dimensions as a major threat to public health. Consequently, there is a pressing need to find effective alternative therapies and therapeutic agents to combat drug-resistant pathogens. Photodynamic therapy (PDT), largely employed as a clinical treatment for several malignant pathologies, has also gained importance as a promising antimicrobial approach. Antimicrobial PDT (aPDT) relies on the application of a photosensitizer able to produce singlet oxygen (¹O₂) or other cytotoxic reactive oxygen species (ROS) upon exposure to appropriate light, which leads to cell death after the induced photodamage. Among different types of 2D nanomaterials with antimicrobial properties, phosphorene, the exfoliated form of black phosphorus (bP), has the unique property intrinsic photoactivity exploitable for photothermal therapy (PTT) as well as for PDT against pathogenic bacteria. Full article

(This article belongs to the Special Issue Photodynamic Therapy: Rising Star in Pharmaceutical Applications)

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27 pages, 5672 KiB

Open AccessReview

Photodynamic Therapy-Induced Anti-Tumor Immunity: Influence Factors and Synergistic Enhancement Strategies

by Wenxin Chou, Tianzhen Sun, Nian Peng, Zixuan Wang, Defu Chen, Haixia Qiu and Hongyou Zhao

Pharmaceutics 2023, 15(11), 2617; https://doi.org/10.3390/pharmaceutics15112617 - 11 Nov 2023

Cited by 10 | Viewed by 2246

Abstract

Photodynamic therapy (PDT) is an approved therapeutic procedure that exerts cytotoxic activity towards tumor cells by activating photosensitizers (PSs) with light exposure to produce reactive oxygen species (ROS). Compared to traditional treatment strategies such as surgery, chemotherapy, and radiation therapy, PDT not only [...] Read more.

Photodynamic therapy (PDT) is an approved therapeutic procedure that exerts cytotoxic activity towards tumor cells by activating photosensitizers (PSs) with light exposure to produce reactive oxygen species (ROS). Compared to traditional treatment strategies such as surgery, chemotherapy, and radiation therapy, PDT not only kills the primary tumors, but also effectively suppresses metastatic tumors by activating the immune response. However, the anti-tumor immune effects induced by PDT are influenced by several factors, including the localization of PSs in cells, PSs concentration, fluence rate of light, oxygen concentration, and the integrity of immune function. In this review, we systematically summarize the influence factors of anti-tumor immune effects mediated by PDT. Furthermore, an update on the combination of PDT and other immunotherapy strategies are provided. Finally, the future directions and challenges of anti-tumor immunity induced by PDT are discussed. Full article

(This article belongs to the Special Issue Photodynamic Therapy: Rising Star in Pharmaceutical Applications)

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Other

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17 pages, 1331 KiB

Open AccessEditor’s ChoiceSystematic Review

Influence of Photosensitizer on Photodynamic Therapy for Peri-Implantitis: A Systematic Review

by Thaís B. M. O. Schweigert, João P. R. Afonso, Renata K. da Palma, Iransé Oliveira-Silva, Carlos H. M. Silva, Elias Ilias Jirjos, Wilson Rodrigues Freitas Júnior, Giuseppe Insalaco, Orlando A. Guedes and Luís V. F. Oliveira

Pharmaceutics 2024, 16(3), 307; https://doi.org/10.3390/pharmaceutics16030307 - 22 Feb 2024

Cited by 1 | Viewed by 1563

Abstract

The treatment of peri-implantitis is challenging in the clinical practice of implant dentistry. With limited therapeutic options and drug resistance, there is a need for alternative methods, such as photodynamic therapy (PDT), which is a minimally invasive procedure used to treat peri-implantitis. This [...] Read more.

The treatment of peri-implantitis is challenging in the clinical practice of implant dentistry. With limited therapeutic options and drug resistance, there is a need for alternative methods, such as photodynamic therapy (PDT), which is a minimally invasive procedure used to treat peri-implantitis. This study evaluated whether the type of photosensitizer used influences the results of inflammatory control, reduction in peri-implant pocket depth, bleeding during probing, and reduction in bone loss in the dental implant region. We registered the study in the PROSPERO (International Prospective Register of Systematic Review) database. We searched three main databases and gray literature in English without date restrictions. In vivo randomized clinical studies involving individuals with peri-implantitis, smokers, patients with diabetes, and healthy controls were included. PDT was used as the primary intervention. Comparators considered mechanical debridement with a reduction in pocket depth as the primary outcome and clinical attachment level, bleeding on probing, gingival index, plaque index, and microbiological analysis as secondary outcomes. After reviewing the eligibility criteria, we included seven articles out of 266. A great variety of photosensitizers were observed, and it was concluded that the selection of the most appropriate type of photosensitizer must consider the patient’s characteristics and peri-implantitis conditions. The effectiveness of PDT, its effects on the oral microbiome, and the clinical patterns of peri-implantitis may vary depending on the photosensitizer chosen, which is a crucial factor in personalizing peri-implantitis treatment. Full article

(This article belongs to the Special Issue Photodynamic Therapy: Rising Star in Pharmaceutical Applications)

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