Репозиторий Университета

© 2020 Elsevier B.V. Background: The present study focuses on investigation of Intra-articular PDT mechanisms for OA treatment. Also, a search for determination of the most effective dose of chlorin e6 (Ce6) for anti-inflammatory PDT of OA was carried out. Methods: The study was carried out on laboratory animals (11 Chinchilla rabbits, 1 year, 2.5 kg) with a gonarthritis model of post-traumatic OA. According to the instructions for using Photoditazin (Ce6 based PS) for PDT of human oncological and non-oncological diseases, the recommended dose is 0.7–1.2 mg/kg. For studies on rabbits, taking into account the conversion coefficient (3.2), the PS doses of 2.4, 3.2 and 6.4 mg/kg were selected. Fluorescence spectra were measured intra-articular before and after PDT using spectrometer with fiber-optic probe. The intrajoint PDT was carried out using a laser (662 ± 10 nm) and a fiber-optic catheter with a cylindrical diffuser inside a sapphire needle for a uniform distribution of the laser radiation. The immunohistochemical study was carried out by staining the samples with caspase-3. Results: Histological and immunohistochemical analysis showed that the best PS dose for intravenous administration for PDT of rabbit gonarthritis is 3.2 mg/kg. The PS concentration directly in the synovial tissue was 0.5 mg/kg, and this was enough to achieve the most positive results to reduce the caspase-3 level. Conclusion: The caspase-3 level correlates well with other signs of inflammation in the synovial membrane (edema, etc.). Therefore, to assess the PDT effectiveness in the treatment of gonarthritis accompanied by synovitis, it is sufficient to analyze only for caspase-3. The efficacy of PDT with Ce6 showed that 3.2 mg/kg PS dose (1 mg/kg for a human) is the most effective.

© 2020 Elsevier B.V. Background: The present study focuses on investigation of Intra-articular PDT mechanisms for OA treatment. Also, a search for determination of the most effective dose of chlorin e6 (Ce6) for anti-inflammatory PDT of OA was carried out. Methods: The study was carried out on laboratory animals (11 Chinchilla rabbits, 1 year, 2.5 kg) with a gonarthritis model of post-traumatic OA. According to the instructions for using Photoditazin (Ce6 based PS) for PDT of human oncological and non-oncological diseases, the recommended dose is 0.7–1.2 mg/kg. For studies on rabbits, taking into account the conversion coefficient (3.2), the PS doses of 2.4, 3.2 and 6.4 mg/kg were selected. Fluorescence spectra were measured intra-articular before and after PDT using spectrometer with fiber-optic probe. The intrajoint PDT was carried out using a laser (662 ± 10 nm) and a fiber-optic catheter with a cylindrical diffuser inside a sapphire needle for a uniform distribution of the laser radiation. The immunohistochemical study was carried out by staining the samples with caspase-3. Results: Histological and immunohistochemical analysis showed that the best PS dose for intravenous administration for PDT of rabbit gonarthritis is 3.2 mg/kg. The PS concentration directly in the synovial tissue was 0.5 mg/kg, and this was enough to achieve the most positive results to reduce the caspase-3 level. Conclusion: The caspase-3 level correlates well with other signs of inflammation in the synovial membrane (edema, etc.). Therefore, to assess the PDT effectiveness in the treatment of gonarthritis accompanied by synovitis, it is sufficient to analyze only for caspase-3. The efficacy of PDT with Ce6 showed that 3.2 mg/kg PS dose (1 mg/kg for a human) is the most effective.

© 2017 Elsevier B.V. The use of polymeric carriers to deliver hydrophobic photosensitizers has been widely discussed as a way to improve both fluorescence diagnostic and photodynamic therapy (PDT) of cancers; however, the photophysical and pharmacokinetic parameters, as well as the PDT activity, of such modifications have, until now, only been poorly investigated. The purpose of the present study was to explore the efficacy of PDT with the formulation of the photosensitizer chlorin e6 (Ce6) in combination with polyvinyl alcohol (PVA) in comparison with Ce6 alone and with the clinical drug, Photodithazine in a mouse tumor model. We also investigated the photoactivity of the Ce6-PVA in a model reaction of tryptophan oxidation, analyzed the polymer–Ce6 interaction using fluorescence spectroscopy and atomic-force microscopy, and tested the phototoxicity in vitro. Using fluorescence imaging in vivo we found that injection to mice of Ce6 in a formulation with PVA resulted in a higher tumor-to-normal ratio and greater photobleaching when compared with either the use of Ce6 alone, or with the effects of Photodithazine. Tumor growth study and histological examination of CT26 tumors revealed fast, reproducible tumor regression and more advanced necrosis after PDT with Ce6-PVA. The higher photoactivity of the Ce6-PVA complex was confirmed in a model reaction of tryptophan oxidation and in cultured cells. Therefore, encapsulation of Ce6 in PVA represents a promising strategy for further increasing the selectivity and efficacy of PDT.