Search

The aim of this study was to analyze the immediate and long-term results of using photodynamic therapy (PDT) in patients with leukoplakia of the oral mucosa. The retrospective study included 223 patients with morphologically verified leukoplakia of the oral mucosa. Patients received treatment at the hyperthermia and photodynamic therapy department from 2013 to 2023. The average age was 51.9±8.9 years. Clinically, 211 patients (94.6%) had a flat form of the disease, 12 patients (5.4%) had a verrucous form. The photosensitizer (PS), based on chlorin e6, was administered intravenously once in doses of 1.7 to 2.5 mg/kg body weight. Irradiation of pathologically changed lesions was carried out 2-2.5 hours after the end of its infusion, using a semiconductor laser device “UPL PDT”, with a wavelength λ=665±5 nm. The laser radiation dose density varied from 25 to 100 J/cm², the power density from 0.07 to 0.32 W/cm², the duration of one irradiation field - from 2 to 13.5 minutes, depending on its linear dimensions. The severity of adverse reactions was assessed on days 1-30 after treatment using the CTCAE 4.03 scale. The immediate results of treatment were assessed up to 3 months after PDT, with morphological confirmation of the response to treatment. No serious adverse reactions were observed during PS infusion and irradiation. No symptoms of dermal phototoxicity were reported. During control examinations, up to 3 months after irradiation in patients with flat and verrucous forms, the frequency of complete regressions was 97.1% (n=205) and 58.3% (n=6) cases, partial regressions - 2,9% (n=7) and 25% (n=3) of cases, respectively. Objective response rates were observed at 100% and 83.3%, respectively. The period of observation of patients varies from 3 to 120 months. (average 66 months). The frequency of disease relapses during this period was 9%. Patients with partial regression and identified relapse were treated with repeated PDT sessions. PDT is a well-tolerated and effective treatment method for patients with leukoplakia of the oral mucosa, which has significant advantages over traditional methods of treating this precancerous pathology. These include minimal toxicity to the normal tissues surrounding the pathological foci due to the selective accumulation of PS in leukoplakia tissues, a slight risk of serious adverse reactions, the possibility of an outpatient session, the possibility of repeated treatment over a large area of damage and good cosmetic results).

A significant therapeutic effect of photodynamic therapy (PDT) is shown in a patient with extensive vulvar cancer after ineffective surgical and chemoradiotherapy. During the year, three courses of local PDT with a photosensitizer based on chlorin e6 were carried out. The photosensitizer was administered intravenously three hours before irradiation at a dose of 1.2 mg/kg. For laser irradiation (662 nm) of the vulvar tumor, a light guide for external irradiation was used: the power density was 0.2 W/cm2, the light dose was from 100 to 250 J/cm2. As a result of treatment, tumor regression and stable remission are observed. The patient remains under observation.

Photodynamic therapy (PDT) is one of the most effective treatments for basal cell skin cancer (BCC). As the incidence rate of BCC is increasing worldwide, interest in developing new methods for diagnosing and treating this disease, taking into account long-term cosmetic results, is growing. The review article presents the results of domestic and foreign studies on the treatment of BCC with PDT. The presented results of studies from various domestic and foreign clinics indicate the high efficiency of independent PDT and a combination of PDT with other treatment methods. PDT is proposed to be used in combination with surgical methods and radiation therapy, immunomodulating and chemotherapeutic agents, and inhibitors of molecules involved in the carcinogenic process. These new strategies open the way to increasing the effectiveness of treatment and prevention of BCC. Moreover, in all studies, the safety of this non-invasive treatment, a low level of adverse reactions during therapy, good tolerance for the patient and excellent cosmetic treatment results are noted. The guidelines currently being developed in Europe and the United States provide consistent expert advice that reflects current published evidence of treatment outcomes for BCC using PDT. Moreover, the recommendations emphasize that the treatment plan for patients with “difficult to treat” BCC should be discussed at an interdisciplinary oncological council.

Background. Photodynamic therapy of acute cholangitis involves the introduction of a photosensitizer into the common bile duct and subsequent laser irradiation of the liver. The study of combined laser action on the liver is promising. Purpose of the study. To evaluate in an experiment the effectiveness of photodynamic therapy of acute cholangitis with the introduction of a photosensitizer into the common bile duct and combined laser irradiation of the liver. Material and methods. Acute cholangitis was modeled in rabbits. In the first group, a saline solution was introduced into the common bile duct, in the second and third – "Photolon". Then, in the second group, photodynamic therapy with endocholedocheal laser irradiation of the liver was performed, in the third group – with combined irradiation. The general condition of the animals, their laboratory, microscopic and microbiological parameters were evaluated. After the autopsy, a histological examination of the liver and common bile duct was performed. Results. On the 2nd day of the experiment, all rabbits developed acute cholangitis. After treatment in the group "Experience 3", in comparison with other groups, there was a greater decrease in the indicators of inflammation and cholestasis in the blood, the number of microorganisms and white blood cells in the bile. In the first group, the formation of liver abscesses was histologically noted. Pathological changes in the wall of the common bile duct and liver in the third group were less pronounced than in the second. Conclusions. 1. The experimental model allows on the second day to reproduce acute cholangitis in rabbits. 2. Photodynamic therapy with Photolon photosensitizer with combined (endocholedocheal and surface) laser irradiation of the liver has a more pronounced bactericidal effect compared to endocholedocheal irradiation.

Background. Malignant tumors management using conventional treatment modalities is associated with poor outcomes. Objective of the study. To assess photodynamic activity of Photolon as monotherapy, as well as in combination with radio- and chemotherapy in an experiment. Material and methods. The research was done on HeLa monolayer culture (human uterine cervix carcinoma), 97 white random-bred rats with Pliss lymphosarcoma and 42 mice (CBA) with uterine cervix cancer-5 (UCC-5). Results. The amplification factor in Photolon photoirradiation was 65.1 in terms of the cytostatic effect and 98.5 in terms of cytotoxic effect. Photodynamic therapy enhances the efficacy of radiotherapy, since it reduced Pliss lymphosarcoma growth rate in rats down to 33.7% and UCC-5 growth rate in mice down to 14.9% of the intact control level (p

The aim of study is to evaluate the tolerability and effectiveness of photodynamic therapy as an organ‑preserving treatment in patients with vulvar leukoplakia. 50 patients with a verifed diagnosis of «vulvar leukoplakia» were included in the study. The age varied from 27 to 74 years. The method of treatment assumed the use of the photosensitizer рhotolon (RUE «Belmedpreparaty», Belarus) administered intravenously in doses of 1.8–2.5 mg/kg. Photoirradiation of pathological foci was carried out 2.5–3 hours after intravenous injection of photolon® using a semiconductor laser «UPL PDT» (LEMT, Belarus, λ=661 nm) at exposure doses from 30 to 100 J/cm2 with a power density of 100–170 mW/cm2. The treatment was performed under medical anesthesia. The results of treatment were evaluated using clinical data. Adverse reactions and complications after the introduction of the photosensitizer and photoirradiation have not been observed. Complete clinical regression of the treated pathological foci was noted in 100% of cases with a follow‑up observation 1 month after the treatment. At follow‑up after 3 months, local recurrences of the disease were detected in 4 cases, which were successfully treated with repeated photo‑dynamic therapy sessions. The percentage of complete regressions was 92%, partial – 8%. The obtained results allow judging on the possibility of using photodynamic therapy in the treatment of patients with vulvar leukoplakia, which allows to preserve the organ and obtain a satisfactory functional and cosmetic result.

The article shows possibilities in fluorescence imaging of malignant skin tumors with chlorin series photosensitizers (PS) photolon and fotoditazin. The regularities of photosensitizer accumulation from the data of local fluorescence spectroscopy depending on the PS and its dose, the clinical picture and the histological form of the malignant skin neoplasm is investigated. It is shown that the level and selectivity of PS accumulation in the tumor focus depends on the PS dose. In studies on 10 patients with basal cell skin cancer after the introduction of fotoditazin at a dose less than 1 mg/kg, fluorescent contrast between tumor and healthy tissue varied between 1.3 and 9.5, the average was 2.8±0.3; for patients who had the administered fotoditazin dose of 1 mg/kg, fluorescent contrast was 2.9±0.4, varying from 1.4 to 5. In a study with 127 patients after the introduction of photolon in the dose of 0.7-1 mg/kg, the average value of the fluorescence intensity in relative units in the intact skin was 6.9±0.3 (min 4.6, max 12.2), at a dose of 1.1 to 1.4 mg/kg – 8.0±0.3 (min 4.6, max 12.5), at a dose of 1.5-2 mg/kg – 9.9±0.7 (min 5.7, max 20.3). It is also shown that fluorescence intensity of malignant neoplasm of the skin with the same dose of the photosensitizer depends on the neoplasm’s clinical and histological forms. So, 3 hours after the introduction of photolon at a dose of 1.3 mg/kg the average fluorescent contrast in the surface type of skin cancer was 2.7±0.5, in the nodal form – 2.3±0.2, in erosive-ulcerative form – 3.6±0.3. In patients with nodular form of squamous skin cancer after the introduction of photolon at a dose of 1.3 mg/kg fluorescent contrast was significantly higher (p

The article is devoted to the development and evaluation of the effi ciency of photodynamic therapy (PDT) with photosensitizer photolon with additional interstitial laser irradiation in patients with head and neck basal cell skin cancer (BCSC). Treatment was performed in 55 patients. On the fi rst stage, all patients underwent photodynamic therapy with interstitial irradiation using fl exible optical fi bers with cylindrical diffuser, on the second stage PDT with distant delivery of laser at a dose of 50-300 J/cm2 was carried out. During the follow- up period of 6 months to 4 years in 13 (23.6%) of the 55 patients a recurrence of the disease was diagnosed. A higher rate of recurrence was in the group of patients who underwent PDT for recurrent neoplasms compared with patients with primary disease (37.5% and 4.3%, respectively), in patients with endophytic growth of the tumor compared to patients with exophytic component (30.0% and 16.0%,respectively) and in patients with large tumors (up to 2.0 cm – 14.3%, from 2.0 to 5.0 cm – 16.7% and more than 5.0 cm – 54.4%).

Cholangiocellular cancer (CCC) is an oncological disease of the bile ducts characterized by a high mortality rate. To date, the use of standard methods for the diagnosis and treatment of CCC has not been able to reduce mortality from this disease. This work presents the results of fluorescence diagnostics (FD), which consists in using a modified optical fiber and photodynamic therapy (PDT) using a therapeutic laser instead of a low-intensity laser. This technique was tested on 43 patients in a clinical setting. The results obtained indicate a direct correlation between spectroscopic and video FD methods. Furthermore, a direct correlation was found between the photobleaching of a chlorin e6-based photosensitizer, with the commercial names of Photolon Radachlorin and Photoran and stricture regression. Our findings demonstrate the possibility of using a therapeutic laser with a wavelength of 660 nm for both diagnosis and treatment of bile ducts cancer, which results in a significant reduction of the operation time without decreasing its effectiveness. [ABSTRACT FROM AUTHOR]

The short-term and long-term outcomes of treatment in 130 patients with basal cell carcinoma (T1N0M0, I stage) using photodynamic therapy with photosensitizer photolon based on chlorine e6 are represented in the article. The session of photodynamic therapy was performed 2.5-3 h after intravenous injection of photolon at dose of 2-2.5 mg/kg using semiconductor laser (λ=660±5 nm, laser power density — from 0.1 to 0.52 W/cm2, light dose — from 50 to 300 J/cm2). Complete regression of primary and recurrent carcinomas was observed in 90.9% and 88.9% of patients, respectively. For follow-up period of 3 to 76 months the local recurrence of the tumor was in detected in 6.9% of cases. Patients, who followed the light regimen for 2–3 days after photolon administration avoiding direct sun light exposure, had no manifestation of phototoxicity. Ten patients who failed to follow the light regimen had mild hyperemia, itching and burning in the exposed skin area selflimiting in several hours. Cosmetic results of photodynamic therapy with photolon are superior to those for traditional treatment methods for this disease.

The new method of photodynamic therapy for basal cell skin carcinoma with intralesional injection of photolon (at dose of 1.44-2.50 mg/cm3 of tumor volume 15 min before irradiation) was developed in the department of dermatology, venerology and dermatooncology in The State Budgetary Healthcare Institution of Moscow Area Moscows regional research clinical institute n.a. M.F. Vladimirskiy. The efficacy of the developed method was evaluated in clinical studies in 30 patients comparing with the group of 32 patients who had conventional PDT with typical intravenous injection of photolon (at dose of 2.0–2.5 mg/kg of body weight 3 h before irradiation). The characteristics of irradiation were the same both in the study and in the control groups: power density of 0.31-0.47 W/cm2, light dose of 300 J/cm2. Compared PDT regimens had similar efficiency. As a result of the performed treatment complete tumor regression was achieved in 93.3% patients with intralesional injection of photolon and in 90.6% patients with intravenous injection. The rate of patients with 2-year recurrence-free survival after intralesional injection of photolon accounted for 96.7%; after intravenous injection – 93.8%. However, the developed method demonstrated superior safety comparing with intravenous injection of photolon: such as there was no need for light regimen after intralesional injection of photolon, there were no cases of skin phototoxicity (12.5% for intravenous injection), no increasing of transaminases (37.5% for intravenous injection).

The results of photodynamic therapy (PDT) in 76 patients with tumors of different sites and with regional or distant metastases are represented. Sixty three patients were under combined or multimodal therapy, 13 patients had systemic PDT as monotherapy. The technique of PDT was as follows: the solution of photosensitizer photolon was administered intravenously at dose of 0.8–1.4 mg/ kg body weight. Laser blood irradiation was performed simultaneously (wavelength of 662 nm, output power of 20 mW, irradiation time of 50 min). Stabilization of the disease defined as the absence of new tumor foci was observed in 55% of treated patients: among them in 47% of patients with disseminated melanoma during 6–10 months after treatment, in 65% patients with breast cancer – for 3–6 years after treatment, and also in 100% of patients with cancer of other sites (colorectal, pancreatic, cervical, ovarian, lung and stomach cancer, retroperitoneal neuroblastoma) – for 10–12 months after treatment. According to ultrasound data the shrinkage of most of metastases up to its complete disappearance was observed. The authors consider that effects of systemic PDT are due to decrease of circulating tumor cells in blood and also due to beneficial impact of this modal of treatment on immune status of cancer patient. Intravenous PDT was shown to improve treatment results and quality of life in patients with metastases of malignant tumors. The approved technique is of considerable interest and requires further investigation of its efficiency including its combination with methods of combined and multimodal treatment.

This article is dedicated to clinical experience of photodynamic therapy (PDT) in Medical Radiological Research Center. Authors represent the results of treatment in 156 patients with primary untreated tumors of different localizations as follows: basal cell skin cancer (BCSC) in 156 patients, squamous cell carcinoma of the skin (SCCS) in 24 patients, cancer of upper and lower lips in 30 patients. The other group of patients included recurrent and metastatic diseases: recurrent BCSC were in 127 patients, recurrent or continued growth of SCCS – in 27, recurrent or continued growth of lip cancer – in 13, intracutaneous metastases of skin melanoma (62 patients) and breast cancer (46) – in 108. PDT was performed with photosensitizers Photosense (2.0 mg/kg), Photolon (0.9–2.5 mg/kg), and Photoditazine (0.7–0.8 mg/kg). The light irradiation dose was 100–600 J/cm2. After PDT of previously untreated BCSC the complete regression (CR) of tumor lesions was in 96.8% of patients, partial regression (PR) – in 3.2% of patients; for PDT of recurrent BCSC in 76.4% and 23.6%, respectively. After PDT treatment in patients with previously untreated SCCS CR of tumor lesions was achieved in 91.7% of patients, PR – in 8.3% of patients. For treatment of relapses in SCCS CR was achieved in 59.3% of cases, PR – in 33.3%, absence of regression was reported in 7.4% of cases. PDT of intracutaneous metastases of skin melanoma and breast cancer provided positive treatment effect (CR + PR + stabilizing) in 95 and 98% of cases, respectively. CR in primary lip cancer after PDT was reported in 86.0% of patients, PR – in 14.0%. For PDT of recurrent lip cancer CR accounted for 69.2%, PR – 30.8%.

Background Among modern methods of tumor diagnosis, fluorescent methods are considered one of the most prospective. Diagnostic agents (DAs) spread throughout the body by the bloodstream, so, the DA molecules are often transported by albumins and can be affected by these proteins. In our study we evaluate the effect of complex formation between bovine serum albumin (BSA) and three fluorescence DA’s (Photolon, Photoditazin and Dimegin) on their fluorescent quantum yields. Methods Electron absorption spectroscopy and fluorescence spectroscopy were carried out to calculate fluorescence quantum yields of the DAs using Rhodamine 6G as a standard fluorescent dye. Results For all three DA’s dissolved in phosphate buffer with pH 7.5 (close to that of blood) the addition of albumin resulted in bathochromic shift of the Soret band as well as change of amplitudes of absorption bands. Similar changes were observed for fluorescence spectra of all DAs that are connected with complex formation between DA and albumin. The presence of isobestic point suggests that DA can present in the solution only in two states, free and BSA-bound. Chlorine-based DA’s demonstrate about 1.5-times higher fluorescence quantum yield in PBS than Dimegin. Nevertheless, the addition of BSA to the solutions of all DA’s decreases sharply their fluorescence quantum yield to approximately equal values. Conclusion The complex formation between DA and albumin equalize fluorescence efficacies of all studied DAs, so the results of photodymanic diagnostics using the specific DA will depend on other factors. [ABSTRACT FROM AUTHOR]

Background Contemporary medicine does not concern the issue of dosimetry in photodynamic diagnosis (PDD) but follows the photosensitizer (PS) producers recommendation. Most preclinical and clinical PDD studies indicate a considerable variation in the possibility of visualization and treatment, as e.g. in case of cervix lesions. Although some of these variations can be caused by the different histological subtypes or various tumor geometries, the issue of varying PS concentration in the tumor tissue volume is definitely an important factor. Therefore, there is a need to establish the objective and systematic PDD dosimetry protocol regarding doses of light and photosensitizers. Methods Four different irradiation sources investigated in PDD (literature) were used for PS excitation. The PS luminescence was examined by means of the non-imaging (spectroscopic) and imaging (wide- and narrow-field of view) techniques. The methodology for low-level intensity photoluminescence (PL) characterization and dedicated image processing algorithm for PS luminescence images analysis were proposed. Further, HeLa cells' cultures penetration by PS was studied by a confocal microscopy. Results Reducing the PS dose with the choice of proper photoexcitation conditions decreases the PDD procedure costs and the side effects, not affecting the diagnostic efficiency. We determined in vitro the minimum incubation time and photosensitizer concentration of Photolon for diagnostic purposes, for which the Photolon PL can still be observed. It was demonstrated that quantification of PS concentration, choice of proper photoexcitation source, appropriate adjustment of light dose and PS penetration of cancer cells may improve the low-level luminescence photodynamic diagnostics performance. Conclusions Practical effectiveness of the PDD strongly depends on irradiation source parameters (bandwidth, maximum intensity, half-width) and their optimization is the main conditioning factor for low-level intensity and low-cost PDD. [ABSTRACT FROM AUTHOR]

A case of successful photodynamic therapy (PDT) of the patient with grade 3 vulvar dysplasia. One course of treatment with photolon was performed. The photosensitizer was administered intravenously as 30 min infusion in dose of 1.0 mg/kg body weight. The PDT session was performed 3h after infusion of photolon, the light dose was 350 J/cm2. The treatment was well tolerated. Due to PDT a complete tumor regression was achieved. The patient received a strict follow-up schedule, for 8 months after PDT no recurrence was observed.

A case of successful photodynamic therapy in patient of 86 y.o. with diagnosis: angiosarcoma of right temporal-parietal region stage IIA (Т2вN0M0) is reported. The tumor was as soft tissue round shape lesion with tuberous contours 3.4х3.4х1.1 cm in size, located in subcutaneous tissue in right parietal region with no scull bone invasion. The patient was refused to surgical treatment with general anesthesia due to severe cardiovascular co-morbidity. The patient underwent a course of photodynamic therapy with Photolon. The photosensitizer was intravenousely introduced for 3 h before irradiation at dose of 1 mg/kg body weight. The parameters of irradiation were as follows: output power – 0.8 W, light dose – 150 J/cm2, 4 irradiation fields 2.5 cm in diameter. During the irradiation there were moderate pain which did not require drug management. After PDT complete regression of the tumor was achieved. For nowadays (11 months after treatment) the patient is observed with no recurrence. The reported case shows that photodynamic therapy may be successfully used for alternative treatment of soft tissue angiosarcoma in patients with no ability for surgical treatment.

Results of treatment for cutaneous metastasis of breast cancer with photjdynamic therapy are represented. The study included 46 patients, the total number of treated cutaneous metastases was 535. For photodynamic therapy photosensitizer photolon given intravenously at a dose of 0.9–1.6 mg/kg body weight 3 h before treatment session (wave length 661±1 nm, плотность мощности 0,11–0,56 J/cm2), мощность на выходе волокна 0,3–2,0 Wt, light dose 50–600 J/cm2. Complete regression of metastasis was obtained in 33.6% of cases, partial – in 39.4%, stabilization – in 22.6%, progression of disease was in 4.3% of cases. The results show the perspectiveness of photodynamic therapy for metastasis as one of the step of treatment.

We have studied the feasibility of using an indotricarbocyanine dye as a marker for the efficacy of photodynamic therapy (PDT) of cancers with the photosensitizer Photolon. We have established that on exposure to laser emission at λ = 667 nm with an exposure dose of 100 J/cm, we observe that the Photolon concentration drops by about a factor of two in the exposed part of the tumor, while the concentration of the indotricarbocyanine dye does not change in any region of the tumor node. We have observed a correlation between the change in the shape of the fluorescence spectra of the indotricarbocyanine dye in vivo in the 780-880 nm resulting from a PDT session with the photosensitizer Photolon and the extent of damage to the tumor tissues. Changes in the shape of the fluorescence spectrum of the dye are interpreted in terms of a model involving the appearance of absorption by different forms of hemoglobin, and changes in their ratio in the exposed part of the tumor due to consumption of molecular oxygen. [ABSTRACT FROM AUTHOR]

The results of treatment of the patient with verrucous luekoplakia of mucous membrane of body of the tongue with photodynamic therapy are represented. In 2015 the patient underwent 4 courses of photodynamic therapy with photosensitizer photolon. Photolon was injected at dose of 2 mg/kg 3 h before irradiation (laser output power was 0.262 W, light dose – 50 and 100 J/cm2). The result of treatment was assessed as complete regression: 4 months after multiple-course photodynamic therapy there were no clinical and histological signs of luekoplakia.

The application of spectroscopic study, microscopic and AFM imaging for examination of fiberoptic applicators is presented. The potential carriers of photoactive agents for photodynamic medicine in form of sol-gel coatings of fiberoptic applicators, are proposed. Optical and morphological properties of the proposed sol-gel coatings doped with photosensitizer Photolon, are characterized. The influence of pH and oxygen changes on entrapped Photolon properties, was examined, as well. The morphology of the applicator coating was examined by using atomic force microscopy. The light distribution from an applicator was studied by means of computer aided image analysis. [ABSTRACT FROM AUTHOR]

A precise and reproducible method of quantitative determination of the photosensitizer (PS) Photolon in liver samples of laboratory animals by means of a spectrophotometric assay with preliminary extraction has been developed. Conditions of the PS extraction have been optimized and validated for the quantitative determination of the PS Photolon by the spectrophotometric assay and the main analytical characteristics have been investigated. Using the method of quantitative determination of the PS Photolon in liver tissue samples a quantitative estimation of in vivo fluorescence of the liver tissue was performed after PS administration to animals. There was a high correlation ( R = 0.99) between results obtained by spectrophotometry ex vivo and spectrofluorimetry in vivo. The method of fluorescence detection in vivo is applicable for studies of the pharmacokinetics of different photosensitizers. [ABSTRACT FROM AUTHOR]

Abstract: It is recognized that chlorin e6–polyvinylpyrrolidone (Ce6–PVP) formulations are characterized by a high efficacy in photodynamic therapy of malignant tumors. Currently, a commercially available formulation of this type is Photolon® (Fotolon®) with Ce6:PVP=1:1 (w/w) and the weight-average molecular weight of PVP is 1.2×104. To gain a better understanding of the role played by PVP in Ce6–PVP formulations, we carry out experiments on IR and UV–VIS absorption, steady-state and time-resolved fluorescence, time-resolved triplet–triplet absorption, octanol–water partitioning, and solubility of chlorin e6 in buffer solutions at pH 6.3, 7.4, and 8.5 in presence of PVP with Ce6:PVP ratios ranging from 1:0 to 1:1000 (w/w) for PVP samples with weight-average molecular weights of 8×103, 1.2×104, and 4.2×104. We show that Ce6 interacts with PVP by forming molecular complexes via hydrophobic interactions and determine the Ce6–PVP binding constant, as well as the mean number of PVP monomers per binding site. We find that complexation of Ce6 with PVP prevents Ce6 aggregation in aqueous media and leads to an enhancement of Ce6 fluorescence quantum yield, while keeping the quantum yield of the intersystem crossing essentially unchanged. Possible scenarios of how the presence of PVP can favorably affect the PDT efficacy of chlorin e6 in Ce6–PVP formulations are discussed. [Copyright &y& Elsevier]

Abstract: Photolon is one of the new photosensitisers that has found application in photodynamic therapy (PDT). Its chemical structure has a partially reduced porphyrin moiety and its molecular structure is comparable to chlorin e6, which can be isolated after hydrolysis of the 5-membered exocyclic β-ketoester moiety of pheophorbide a. For this study, a Photolon doped sol–gel matrix was produced in the form of coatings deposited on silica fibers cores. The material was produced from sols prepared from the silicate precursor TEOS mixed with ethyl alcohol. The sol–gel films were prepared with factor R =20, where R denotes the solvent-to-precursor molar ratio. Hydrochloric acid was added as a catalyst in the correct proportion to ensure acid hydrolysis (pH ≈2). The mixture was stirred at room temperature for 4h using a magnetic stirrer (speed 400rpm). The coated fibers were examined in different environments, liquid and gaseous, at different pH values and with various zinc cation concentrations. The chemical reactions were studied by means of spectroscopic methods, whereby the fluorescence response was studied. It was demonstrated that Photolon immobilized in a sol–gel matrix is accessible for the environment and shows visible response to the external changes. Furthermore, it was observed that these reactions are reversible. These biomaterials are also examined as carriers for PDT. It was also proved that a toxic effect is observed an environment with microorganisms, meaning that doped coatings have photodynamic activity. [Copyright &y& Elsevier]

Abstract: The tetrapyrrolic compound chlorin e6 is currently used as a pharmaceutical substance for Photolon formulation, which is utilized in photodynamic therapy of various diseases. It was found that chlorin e6 could contain both process- and degradation-related impurities. In order to understand their origin, the most abundant impurities were prepared by liquid extraction, preparative chromatography or chemical synthesis. By means of HPLC-PDA–MS, 1D and 2D NMR spectroscopy, these impurities were identified as chlorin e6 174-ethyl ester, chlorin e4, 15-hydroxyphyllochlorin, rhodochlorin, 151-hydroxymethylrhodochlorin δ-lactone, rhodochlorin-15-oxymethyl δ-lactone, rhodochlorin-15-oxymethyl δ-lactone 174-ethyl ester, 151-hydroxymethylrhodoporphyrin δ-lactone, rhodoporphyrin-15-oxymethyl δ-lactone and purpurin 18. The possible routes of formation of the chlorin derivatives upon the production and storage of chlorin e6 are discussed. [Copyright &y& Elsevier]

Abstract: The study was carried out on Escherichia coli strains isolated from poultry and cows. The bacteria were incubated and treated by Photolon, a plant-based photosensibilizator, and exposed after that to laser light at 662nm. Additionally, the photosensitizer was immobilized in fiberoptic sol–gel coating, constructed as an 8-layer applicator. It was demonstrated that Photolon inhibits bacteria growth. Photolon entrapped into the sol–gel matrix also exhibits photodynamic activity and no bacteria were seen near the doped sol–gel applicator. [Copyright &y& Elsevier]

Using the methods of steady‐state absorption and fluorescence spectroscopy and flash‐photolysis, the new photosensitizer “Photolon” (Stock Company “Belmedpreparaty”) and its basic chromophore part — the substance chlorin e6 — have been studied under model conditions. It has been shown that there are no considerable differences between the spectral‐luminescent characteristics of Photolon and chlorin e6 at a concentration not exceeding 2.5·10-5 M in ethanol, phosphate‐saline buffer (pH 8.5), and isotonic solution. That is, the polyvinyl‐pyrrolidone (PVP) entering into the composition of Photolon does not influence the chromophore characteristics being investigated. It has been found that an increase in the mass fraction of PVP in the buffer solution of chlorin e6 leads to an increase in the degree of polarization of chlorin e6 fluorescence and to a change in the spectral‐luminescent and kinetic characteristics, pointing to the fact that the pigment is built into the hydrophobic portions of the polymer. Using the method of multiple scattering of light, it has been shown that both Photolon and chlorin e6 are present in the whole blood of donors and oncological patients mainly in the monomeric form; Photolon is quickly removed from the blood of patients (after 24 h, C ≤ 10-3 mg/ml). [ABSTRACT FROM AUTHOR]

The worldwide increase in bacterial resistance and healthcare-associated bacterial infections pose a serious threat to human health. The antimicrobial photodynamic method reveals the opportunity for a new therapeutic approach that is based on the limited delivery of photosensitizer from the material surface. Nanoporous inorganic–organic composites were obtained by entrapment of photosensitizer Photolon in polysiloxanes that was prepared by the sol–gel method. The material was characterized by its porosity, optical properties (fluorescence and absorbance), and laser-induced antimicrobial activity against Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. The permanent encapsulation of Photolon in the silica coating and the antimicrobial efficiency was confirmed by confocal microscope and digital holotomography. The generation of free radicals from nanoporous surfaces was proved by scanning Kelvin probe microscopy. For the first time, it was confirmed that Kelvin probe microscopy can be a label-free, noncontact alternative to other conventional methods based on fluorescence or chemiluminescence probes, etc. It was confirmed that the proposed photoactive coating enables the antibacterial photodynamic effect based on free radicals released from the surface of the coating. The highest bactericidal efficiency of the proposed coating was 87.16%. This coating can selectively limit the multiplication of bacterial cells, while protecting the environment and reducing the risk of surface contamination. [ABSTRACT FROM AUTHOR]

Liposomal technologies are used in order to improve the effectiveness of current therapies or to reduce their negative side effects. However, the liposome–erythrocyte interaction during the intravenous administration of liposomal drug formulations may result in changes within the red blood cells (RBCs). In this study, it was shown that phosphatidylcholine-composed liposomal formulations of Photolon, used as a drug model, significantly influences the transmembrane potential, stiffness, as well as the shape of RBCs. These changes caused decreasing the number of stomatocytes and irregular shapes proportion within the cells exposed to liposomes. Thus, the reduction of anisocytosis was observed. Therefore, some nanodrugs in phosphatidylcholine liposomal formulation may have a beneficial effect on the survival time of erythrocytes. [ABSTRACT FROM AUTHOR]

Background: Liposomes serve as delivery systems for biologically active compounds. Existing technologies inefficiently encapsulate large hydrophilic macromolecules, such as PVP-conjugated chlorin e6 (Photolon). This photoactive drug has been widely tested for therapeutic applications, including photodynamic reduction of atherosclerotic plaque. Methods: A novel formulation of Photolon was produced using "gel hydration technology". Its pharmacokinetics was tested in Sus scrofa f. domestica. Its cellular uptake, cytotoxicity, and ability to induce a phototoxic reaction were demonstrated in J774A.1, RAW264.7 macrophages, and vascular smooth muscle (T/G HA-VSMC) as well as in vascular endothelial (HUVEC) cells. Results: Developed liposomes had an average diameter of 124.7 ± 0.6 nm (polydispersity index (PDI) = 0.055) and contained >80% of Photolon). The half-life of formulation in S. scrofa was 20 min with area under the curve (AUC) equal to 14.7. The formulation was noncytotoxic in vitro and was rapidly (10 min) and efficiently accumulated by macrophages, but not T/G HA-VSMC or HUVEC. The accumulated quantity of photosensitizer was sufficient for induction of phototoxicity in J774A.1, but not in T/G HA-VSMC. Conclusions: Due to the excellent physical and pharmacokinetic properties and selectivity for macrophages, the novel liposomal formulation of Photolon is a promising therapeutic candidate for use in arteriosclerosis treatment when targeting macrophages but not accompanying vascular tissue is critical for effective and safe therapy. [ABSTRACT FROM AUTHOR]