Search Results (87)

Background: Gabapentinoids (gabapentin and pregabalin) are medications used to treat epilepsy and diabetic neuropathy. Reports of gabapentinoid-associated adverse drug reactions (ADRs) are increasing. This study aimed to explore these potential signals, with a focus on ocular adverse effects. Methods: A mixed-methods design was adopted, utilising quantitative and qualitative approaches encompassing: (I) a social listening approach using Reddit; (II) a pharmacovigilance retrospective disproportionality analysis study using serious reports to the FDA Adverse Event Reporting System (FAERS) (2015–2025); and (III) a literature review (2014–2025). Results: Reddit data revealed several user-reported adverse ocular effects, including blurred vision, diplopia and photosensitivity, across 78 and 40 identified reactions for gabapentin and pregabalin, respectively. Pharmacovigilance findings identified positive signals for eye disorders with both gabapentinoids compared to active control diazepam, amitriptyline and carbamazepine). Incidental findings highlighted potential discrepancies between FAERS data and undesired effects listed within the manufacturer’s literature, with pregabalin exhibiting higher reporting odds than gabapentin for cataract (ROR: 4.55; 95% CI: 2.51–8.26) and blindness (ROR: 2.63; 95% CI: 1.85–3.73). The literature review reinforced eye disorder concerns, specifically retinal effects with gabapentinoids, noting the absence of robust, high-quality research. Nevertheless, it identified a plausible biological mechanism involving the CACNA2D1 receptor in retinal cells of animal models, with evidence of an effect following oral administration of pregabalin. Conclusions: This study suggests an increase in eye disorder reports associated with gabapentinoid use. Further clinical and epidemiological studies are warranted to validate these real-world signals. Full article

Hypericin (Hyp) is a naturally occurring photosensitizer (PS) exhibiting a broad spectrum of biological activities. However, its high hydrophobicity significantly limits its medical applicability. This study aimed to develop an efficient method for extracting Hyp from Hypericum perforatum L. biomass and to obtain its water-soluble micellar formulation. A protocol for Hyp isolation from the aerial parts of the plant was established, involving a preliminary defatting step using a Soxhlet apparatus, followed by ultrasonic-assisted extraction with acetone. The water-soluble formulation was prepared via the thin-film hydration method using the nonionic block copolymer Pluronic F-127. The resulting micelles demonstrated colloidal stability, with a mean hydrodynamic diameter of approximately 30 nm. A high Hyp loading efficiency was achieved, with an encapsulation efficiency (EE) of 95.4 ± 2.7%, yielding a concentration of 600.6 ± 16.6 µM within the micellar formulation. In vitro biological studies were performed using the murine GL261 glioblastoma cell line. The micellar Hyp formulation exhibited efficient time-dependent cellular accumulation and photoinduced cytotoxicity, with no observable dark toxicity. The proposed method enables the production of a stable Hyp formulation that retains its photosensitizing properties, thereby opening promising avenues for its application in photodynamic and sonodynamic therapies. Full article

Self-limited focal epilepsies in childhood (SELFEs), formerly referred to as “benign epilepsies in childhood”, constitute a heterogeneous group of epileptic conditions with onset predominantly in the neonatal, infantile, and childhood periods. A defining feature of these syndromes is that seizures arise without underlying structural, metabolic, or other demonstrable cerebral pathology, and the overall clinical trajectory is expected to be favorable, with seizures resolving spontaneously over time. Current nosological frameworks divide SELFEs into two broad categories according to age at onset: (a) neonatal and infantile forms, encompassing self-limited familial and non-familial neonatal, neonatal-infantile, and infantile epilepsies, genetic epilepsy with febrile seizures plus (GEFS+), and myoclonic epilepsy of infancy (MEI); and (b) childhood-onset forms, including self-limited epilepsy with centrotemporal spikes (SeLECTS), self-limited epilepsy with autonomic seizures (SeLEAS), childhood occipital visual epilepsy (COVE), and photosensitive occipital lobe epilepsy (POLE). Despite their historically “benign” label, there is no general agreement to include GEFS + and MEI among the group of SELFEs as both these conditions have been not classified as focal epilepsy in general. Accumulating evidence shows that a subset of affected children subsequently develop additional seizure types, cognitive deterioration, and behavioral or neuropsychiatric difficulties—outcomes that the word “benign” does not adequately communicate. Advances in molecular genetics have identified pathogenic variants affecting ion channels, synaptic transmission, and neuronal excitability, reshaping current understanding of disease mechanisms and phenotypic variability across these syndromes. This review highlights clinically relevant challenges in the diagnosis and management of SELFEs, critically examines emerging genotype–phenotype correlations, and provides evidence-based recommendations for antiseizure medication initiation and withdrawal tailored to individual syndrome characteristics and risk profiles. Full article

Introduction: Type 2 diabetes mellitus predisposes patients to neuropathy, peripheral arterial disease, and diabetic foot ulcers, which may become infected and progress to osteomyelitis, increasing the risk of amputation. The growing prevalence of multidrug-resistant organisms complicates management. Photodynamic therapy (PDT), which combines a photosensitizer with light-emitting diode irradiation to generate reactive oxygen species, has emerged as a potential adjunctive antimicrobial strategy without inducing resistance. Objective: To describe clinical outcomes observed in patients with diabetic foot osteomyelitis treated with adjunctive photodynamic therapy (PDT), with emphasis on wound evolution, limb preservation, and healing time. Methods: This prospective case series included patients with osteomyelitis secondary to infected diabetic foot ulcers treated at a university hospital. Demographic and clinical data were collected from medical records. Serial photographic documentation was used to monitor wound progression and tissue response during therapy. Results: Sixteen patients with diabetic foot osteomyelitis were included. Complete healing was achieved in 13 patients (81.25%), while 2 patients (12.5%) remained under treatment with partial healing and 1 (6.25%) underwent major amputation. Among healed patients, healing time ranged from 19 to 546 days, with a median of 118 days. The number of photodynamic therapy sessions ranged from 2 to 12, depending on the clinical course of each case. Healing time varied among patients, and the hallux was the most frequent site of osteomyelitis. During follow-up, only one patient underwent major amputation, whereas the remaining patients either achieved complete healing or were still under treatment at the time of analysis. Healing time was comparable between insulin-dependent and non-insulin-dependent diabetes, although numerically shorter in the latter. Longer healing periods were associated with more treatment sessions. Conclusions: In this prospective uncontrolled case series, adjunctive PDT was associated with favorable clinical evolution in a subset of patients with diabetic foot osteomyelitis. However, because of the small sample size and the absence of a control group, these findings should be considered preliminary and hypothesis-generating. Full article

Background: Phototherapy utilizes targeted irradiation to inactivate bacteria or treat various medical conditions. Depending on the therapeutic goal, wavelengths from violet to infrared (IR) are applied. Within the visible and near-IR spectrum, photodynamic therapy (PDT) combines light with photosensitizers that generate reactive oxygen species (ROS), leading to bacterial inactivation. Optimizing photodynamic efficacy can involve either enhancing ROS formation through specific topical agents that modulate ROS generation or employing dual-wavelength light irradiation (DWLR) to achieve synergistic excitation. Established DWLR protocols typically combine blue and red light or IR to activate distinct photosensitizers. Materials and Methods: This study investigates whether a similar synergistic effect can be achieved within the green spectral range by simultaneously exciting a single photosensitizer—coproporphyrin III (CP III)—at 496 nm and 547 nm. Results: Convolution analysis and in vitro bacterial reduction experiments with Cutibacterium acnes subsp. elongatum revealed that cyan irradiation (496 nm) achieved the strongest photoreduction (2.31 log steps at 1620 J/cm²), whereas PC-lime irradiation (547 nm) produced a smaller effect (0.74 log steps). DWLR protocols (simultaneous and sequential irradiation) resulted in intermediate reductions (1.64 and 1.73 log steps, respectively), exceeding PC-lime but not surpassing cyan irradiation alone. Conclusions: These findings demonstrate that excitation efficiency at the local absorption maximum of CP III is the primary determinant of ROS generation, while spectral broadening through DWLR does not enhance bacterial inactivation within this wavelength range and in vitro setup. Full article

The challenges associated with solubility and bioavailability of porphyrinoid-type photosensitizers in photodynamic therapy require solutions that are based on modern drug carriers, including polymeric nanoparticles. With that in mind this review discusses poly(lactic-co-glycolic acid, PLGA)-based polymeric nanoparticles encapsulating selected well-known photosensitizers, such as protoporphyrin IX, tetrahydroxyphenylporphyrin, chlorin e6, and tetracarboxyphenylporphyrin, with a view to the physicochemical and biological properties. Also discussed are their potential medical applications towards photodynamic and sonodynamic therapy. PLGA-based nanoparticles, encapsulating photosensitizers, were analysed in terms of particle size, surface charge, morphology, loading efficiency, release kinetics, and stability. Moreover, the cellular uptake and subcellular localisation of carriers were considered in correlation to polymer composition and surface functionalisation. Special attention was given to how PEGylation, lipid-hybrid coatings, or the incorporation of additional therapeutic or imaging agents has modulated both the physicochemical properties and biological activities of photosensitizers. The comparative assessment of different porphyrinoid-based photosensitizers highlighted how hydrophobicity, amphiphilicity, and molecular structure have an influence on encapsulation efficiency and therapeutic outcomes. Furthermore, issues such as the premature release of photosensitizers, along with limited bioavailability, and limited penetration through biological barriers were addressed as well as some proposed mitigation strategies. Overall, this review highlights the versatility of PLGA nanoparticles as a powerful platform for photosensitizer delivery, with promising implications for advancing polymer-based nanomedicine and improving the efficacy of photodynamic therapy. Full article

The issue of antibiotic resistance is becoming increasingly severe, urgently requiring the development of new antibacterial strategies. Photodynamic therapy (PDT) has gradually emerged as a promising alternative due to its spatiotemporal controllability, low risk of drug resistance, and broad-spectrum antibacterial properties. However, most existing photosensitizers (PSs) are hydrophobic, which limits their application efficiency in PDT. To address this problem, we designed and synthesized a water-soluble perylene diimide derivative (PDICN-CBn) as a photosensitizer. By introducing quaternary ammonium salt groups, its water solubility was improved, and antibacterial activity was enhanced. Subsequently, PDICN-CBn was assembled into silk fibroin/polylactic acid (SF/PLA) nanofibrous membranes via electrospinning technology, successfully constructing a visible-light-responsive ternary composite nanofibrous membrane (SF/PLA@PDICN-CBn). Using various characterization methods such as nuclear magnetic resonance (¹H-NMR), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM), the microstructure, chemical composition, and structural characteristics of the nanofibrous membranes were systematically analyzed, verifying the successful synthesis of the photosensitizer and its assembly into the nanofibrous membranes. In the reactive oxygen species (ROS) experiment, electron spin resonance (ESR) spectra showed that PDICN-CBn efficiently generated singlet oxygen (¹O₂), superoxide anion (·O₂⁻), and hydroxyl radical (·OH) under visible light irradiation, confirming its ability to produce different types of ROS through both type I and type II photodynamic reactions. In the antibacterial experiments, Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and methicillin-resistant Staphylococcus aureus (MRSA) were selected for a series of tests, including plate-counting antibacterial assays, bacterial live/dead staining, and SEM observation of morphology. The results showed that 8 μg/mL of PDICN-CBn effectively destroyed the bacterial cell membrane structure and killed bacteria (bactericidal rate > 95%) after 2 h of visible light irradiation. This work successfully developed a novel visible-light-responsive SF/PLA@PDICN-CBn nanofibrous membrane with a dual antibacterial system combining photodynamic and electrostatic adsorption antibacterial properties, providing new ideas and methods for the design and development of photodynamic antibacterial materials. The prepared nanofibrous membrane has potential application values in fields such as wound dressings and medical protective materials and is expected to provide strong support for solving clinical infection problems. Full article

Photoelectrochemical (PEC) biosensors have emerged as a significant research focus in the fields of bioanalysis and medical diagnostics in recent years due to their high sensitivity, low background noise, and ease of miniaturization. This review summarizes the fundamental principles of PEC biosensors, recent advances in photoactive materials, signal amplification strategies, and typical applications. Photoactive materials serve as the source of the sensor signal and can achieve signal enhancement through strategies such as heterostructure construction, localized surface plasmon resonance (LSPR) effects, and defect engineering. PEC sensors have been widely applied in areas such as cancer liquid biopsy and pathogen detection; however, challenges remain, including material biocompatibility, anti-interference capability in complex samples, and lack of standardized platforms. Future development trends include the design of green and low-toxicity photosensitive materials, integration with microfluidic and wearable devices, and artificial intelligence-assisted signal analysis, which will promote the translation of PEC biosensors toward clinical applications and real-time detection. Full article

Background/Objectives: Patients with erythropoietic protoporphyria (EPP) have a decreased activity of the ferrochelatase enzyme which converts protoporphyrin IX (PpIX) into heme, causing PpIX to accumulate in erythrocytes. The ensuing release of PpIX to the skin when exposed to visible light causes a phototoxic reaction with severe pain, erythema, and edema. Erythrocyte PpIX levels in adult EPP patients are rather stable and largely unaffected by pharmaceutical treatments. It is important to be aware of drugs causing an increase in PpIX as this may increase the risk of liver toxicity. Method: The patient had blood samples taken regularly for analyses of PpIX, znPpIX, ALT, ALP, iron, leucocytes, C-reactive protein, and hemoglobin before, during, and after treatment with teriflunomide. Additionally, we tested if teriflunomide increased PpIX in vitro. Results: A female EPP patient was treated for 7 years with teriflunomide for multiple sclerosis attacks. During treatment, her natural PpIX level increased from about 30 µmol/L to about 200 µmol/L, without significant simultaneous changes in hemoglobin, iron levels, alanine transaminase (ALT), or alkaline phosphatase (ALP). The patient experienced no increase in photosensitivity. In vitro addition of teriflunomide did not affect PpIX levels. Discussion: In patients with lead intoxication, the release of PpIX from erythrocytes is very slow. The increase in PpIX during treatment with teriflunomide compared to periods with no medication could be caused by a similar slow PpIX release from the erythrocytes. This theory is supported by the patient’s unchanged light sensitivity and stable levels of hemoglobin, iron, and liver enzymes. Full article

The growing threat of antimicrobial resistance has necessitated the development of alternative, non-antibiotic therapies for effective microbial control. Antimicrobial photodynamic therapy, which uses photosensitizers activated by light to generate reactive oxygen species, offers a promising solution. Among natural photosensitizers, curcumin, a polyphenolic compound from Curcuma longa, has demonstrated broad-spectrum antimicrobial activity through reactive oxygen species-mediated membrane disruption and intracellular damage. However, curcumin’s poor water solubility, low stability, and limited bioavailability hinder its clinical utility. Nanotechnology has emerged as a transformative strategy to overcome these limitations. This review comprehensively explores advances in nanocurcumin- and curcumin-loaded nanoparticles, highlighting their physicochemical enhancements, photodynamic mechanisms, and antimicrobial efficacy against multidrug-resistant and biofilm-associated pathogens. A range of nanocarriers, including chitosan, liposomes, nanobubbles, hybrid metal composites, metal–organic frameworks, and covalent organic frameworks, demonstrate improved microbial targeting, light activation efficiency, and therapeutic outcomes. Applications span wound healing, dental disinfection, food preservation, water treatment, and medical device sterilization. Conclusions and future directions are given, emphasizing the integration of smart nanocarriers and combinatorial therapies to enhance curcumin’s clinical translation. Full article

Photodynamic therapy (PDT) is a non-invasive therapeutic method with over a century of medical use, especially in dermatology, ophthalmology, dentistry, and, notably, cancer treatment. With an increasing number of clinical trials, there is growing demand for innovation in PDT. Despite being a promising treatment for cancer and bacterial infections, PDT faces limitations such as poor water solubility of many photosensitizers (PS), limited light penetration, off-target accumulation, and tumor hypoxia. This review focuses on chlorins—well-established macrocyclic PSs known for their strong activity and clinical relevance. We discuss how nanotechnology addresses PDT’s limitations and enhances therapeutic outcomes. Nanocarriers like lipid-based (liposomes, micelles), polymer-based (cellulose, chitosan, silk fibroin, polyethyleneimine, PLGA), and carbon-based ones (graphene oxide, quantum dots, MOFs), and nanospheres are promising platforms that improve chlorin performance and reduce side effects. This review also explores their use in Antimicrobial Photodynamic Therapy (aPDT) against multidrug-resistant bacteria and in oncology. Recent in vivo studies demonstrate encouraging results in preclinical models using nanocarrier-enhanced chlorins, though clinical application remains limited. Full article

Serious oral infections are frequently caused by Candida species, which have lately demonstrated resistance to antifungal medications. As a result, new therapeutic strategies, like photodynamic therapy (PDT), are desperately needed. Lactoferrin (LF), a salivary enzyme, is a natural protein that binds iron and has antifungal properties. Given its chemical structure and light absorption at 310–350 nm, LF appears to be a good photosensitizer in a PDT process for treating oral candidiasis. The purpose of this work was to assess the effectiveness of lactoferrin (LF) as a photosensitizer (PS) in photodynamic treatment (PDT) against oral multidrug-resistant (MDR) isolates of Candida spp. using an in vitro investigation. For this in vitro investigation, oral MDR isolates of Candida albicans, Candida kruseii, and Candida glabrata were employed. Using a Kirby–Bauer test (Eucast protocol), a solution of 20 mg of bovine lactoferrin dissolved in 1 mL of Sabouraud’s broth was tested in four different experimental combinations: (i) the solution as it is; (ii) the solution activated with 3% H₂O₂; (iii) the solution activated by light at 310–350 nm; and (iv) the solution activated with both 3% H₂O₂ and light at 310–350 nm. A control group and one with only H₂O₂ were also tested. After that, the Petri plates were incubated for 48 h at 37 °C. With inhibitory halos ranging from 30 to 40 mm for all Candida spp. MDR analyzed, group (iv) displayed the greatest results. H₂O₂ + lactoferrin-based solutions are thought to be potential PS in PDT for MDR Candida spp. eradication. Full article

Cancer stem cells (CSCs) are essential for the growth of malignancies because they encourage resistance to cancer therapy and make metastasis and relapse easier. To effectively tackle the obstacles presented by CSCs, novel therapeutic approaches are required. Photodynamic therapy (PDT) is a promising treatment option for cancer cells, which uses light-sensitive medications that are activated by light wavelengths. This review investigates the use of PDT to overcome malignancies driven by CSCs that have innate resistance mechanisms. PDT works by causing tumor cells to accumulate photosensitizers (PSs) selectively. The reactive oxygen species (ROS), which kill cells, are released by these PSs when they are stimulated by light. According to recent developments in PDT, its efficacy may go beyond traditional tumor cells, providing a viable remedy for the resistance shown by CSCs. Researchers want to improve the targeted elimination and selective targeting of CSCs by combining PDT with new PSs and customized delivery systems. Studies emphasize how PDT affects CSCs as well as bulk tumor cells. According to studies, PDT not only limits CSC growth but also modifies their microenvironment, which lowers the possibility of recovery. Additionally, studies are being conducted on the utilization of PDT and immunotherapeutic techniques to improve treatment efficacy and overcome inherent resistance of CSCs. In conclusion, PDT is a viable strategy for treating carcinogenesis driven by CSCs. By applying the most recent advancements in PDT technologies and recognizing how it interacts with CSCs, this treatment has the potential to surpass traditional resistance mechanisms and improve the future of cancer patients. Clinical and preclinical studies highlight that combining PDT with CSC-targeted approaches has the potential to overcome current therapy limitations. Future efforts should focus on clinical validation, optimizing light delivery and PS use, and developing effective combination strategies to target CSCs. Full article

Malignant skin conditions are classified as the most common forms of cancer, with an evolution of one million new cases reported every year. Research efforts in the medical field are focused on developing innovative strategies for the dissemination of measures for preventing cancer and providing new antitumor compounds. The present research examines the development and evaluation of 1% Carbopol-based hydrogels incorporating two porphyrin derivatives—5,10,15,20-tetrakis-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.1) and 5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.2)—to create formulations suitable for topical photodynamic therapy (PDT) applications. The physicochemical properties of the obtained hydrogels were carefully evaluated, revealing the successful integration of the porphyrins into the 1% Carbopol hydrogel matrix. Rheological analysis demonstrated pseudoplastic behavior, with an increase in viscosity properties for P2.1 and P2.2, suggesting interactions with the Carbopol polymer structure. UV-visible and fluorescence spectroscopy confirmed the maintenance of the porphyrins’ photodynamic properties, essential for therapeutic efficacy. Pharmacotechnical studies highlighted the hydrogels’ suitability for topical applications. The formulations maintained an optimal pH range, ensuring skin compatibility and minimizing the potential for skin irritation. Their mechanical properties, including elasticity and rigidity, provided stability during handling and application. The high swelling capacity indicated effective moisture retention, enhancing skin hydration and drug release potential. Furthermore, the hydrogels demonstrated excellent spreadability, enabling uniform application and coverage, crucial for efficient light activation of the photosensitizers. The combination of robust physicochemical and pharmacotechnical properties highlights the potential of these porphyrin-loaded 1% Carbopol hydrogels as promising carriers for topical PDT. These results permit further biological and therapeutic investigations to optimize the formulation for clinical use, advancing the development of effective localized photodynamic therapies. Full article

Background/Objectives: Liposomal drug formulations improve anticancer treatment efficacy and reduce toxicity by altering pharmacokinetics and biodistribution. Indocyanine Green (ICG), an FDA-approved near-infrared imaging agent, exhibits photosensitivity, photothermal effects, and potential ferroptosis induction, enhancing anticancer activity. Doxorubicin (DOX), widely used for treating breast, ovarian, and liver cancers, is limited by cardiotoxicity, requiring dosage control. Incorporating ICG and DOX into liposomes enables medical imaging, controlled drug release, reduced administration frequency, and fewer side effects. This study aims to develop liposomes encapsulating both ICG and DOX and evaluate their theranostic potential in in vitro and in vivo lung adenocarcinoma models. Methods: Liposomes containing ICG and DOX (Lipo-ICG/DOX) were synthesized using an active loading method and characterized for size (~140 nm), lipid, and drug concentrations. In vitro studies using A549 lung cancer cells assessed liposome uptake via fluorescence microscopy, while in vivo xenograft models evaluated therapeutic efficacy. Results: Lipo-ICG/DOX showed uptake in A549 cells, with ICG localizing in lysosomes and DOX in nuclei. Treatment reduced cell viability significantly by day three. In vivo imaging demonstrated the retention of liposomes in tumor sites, with ICG signals observed in the liver and intestines, indicating metabolic routes. When combined with 780 nm light exposure, liposomes slowed tumor growth over 12 days. Mechanistic studies revealed combined ferroptosis and apoptosis induction. Conclusions: Lipo-ICG/DOX demonstrates strong theranostic potential, integrating imaging and therapy for lung adenocarcinoma. This multifunctional formulation offers a promising strategy for improving cancer treatment efficacy while minimizing side effects. Full article