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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">bioph</journal-id><journal-title-group><journal-title xml:lang="ru">Biomedical Photonics</journal-title><trans-title-group xml:lang="en"><trans-title>Biomedical Photonics</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2413-9432</issn><publisher><publisher-name>Non-profit partnership for development of domestic photodynamic therapy and photodiagnosis</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.24931/2413-9432-2017-6-3-16-32</article-id><article-id custom-type="elpub" pub-id-type="custom">bioph-182</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНЫЕ СТАТЬИ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL ARTICLES</subject></subj-group></article-categories><title-group><article-title>ИССЛЕДОВАНИЕ ФОТОСЕНСИБИЛИЗАТОРА  ДЛЯ АНТИБАКТЕРИАЛЬНОЙ ФОТОДИНАМИЧЕСКОЙ ТЕРАПИИ НА ОСНОВЕ ЦИКЛОДЕКСТРИНОВОЙ КОМПОЗИЦИИ МЕТИЛОВОГО  ЭФИРА 133-N-(N-МЕТИЛНИКОТИНИЛ) БАКТЕРИОПУРПУРИНИМИДА</article-title><trans-title-group xml:lang="en"><trans-title>STUDY OF PHOTOSENSITIZER FOR ANTIBACTERIAL PHOTODYNAMIC THERAPY BASED ON CYCLODEXTRIN FORMULATION OF 133-N-(N-METHYLNICOTINYL)BACTERIOPURPURINIMIDE METHYL ESTER</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Меерович</surname><given-names>Г. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Meerovich</surname><given-names>G. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва.</p></bio><bio xml:lang="en"><p>Moscow.</p></bio><email xlink:type="simple">meerovich@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Ахлюстина</surname><given-names>Е. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Akhlyustina</surname><given-names>E. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва.</p></bio><bio xml:lang="en"><p>Moscow.</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Тиганова</surname><given-names>И. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Tiganova</surname><given-names>I. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва.</p></bio><bio xml:lang="en"><p>Moscow.</p></bio><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Панов</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Panov</surname><given-names>V. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва.</p></bio><bio xml:lang="en"><p>Moscow.</p></bio><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Тюкова</surname><given-names>В. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Tyukova</surname><given-names>V. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва.</p></bio><bio xml:lang="en"><p>Moscow.</p></bio><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Толордава</surname><given-names>Э. Р.</given-names></name><name name-style="western" xml:lang="en"><surname>Тolordava</surname><given-names>E. R.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва.</p></bio><bio xml:lang="en"><p>Moscow.</p></bio><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Алексеева</surname><given-names>Н. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Alekseeva</surname><given-names>N. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва.</p></bio><bio xml:lang="en"><p>Moscow.</p></bio><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Линьков</surname><given-names>К. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Linkov</surname><given-names>K. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва.</p></bio><bio xml:lang="en"><p>Moscow.</p></bio><xref ref-type="aff" rid="aff-5"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Романова</surname><given-names>Ю. М.</given-names></name><name name-style="western" xml:lang="en"><surname>Romanova</surname><given-names>Yu. M.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва.</p></bio><bio xml:lang="en"><p>Moscow.</p></bio><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Грин</surname><given-names>М. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Grin</surname><given-names>M. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва.</p></bio><bio xml:lang="en"><p>Moscow.</p></bio><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Миронов</surname><given-names>А. Ф.</given-names></name><name name-style="western" xml:lang="en"><surname>Mironov</surname><given-names>A. F.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва.</p></bio><bio xml:lang="en"><p>Moscow.</p></bio><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Лощенов</surname><given-names>В. Б.</given-names></name><name name-style="western" xml:lang="en"><surname>Loshchenov</surname><given-names>V. B.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва.</p></bio><bio xml:lang="en"><p>Moscow.</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Каприн</surname><given-names>А. Д.</given-names></name><name name-style="western" xml:lang="en"><surname>Kaprin</surname><given-names>A. D.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва.</p></bio><bio xml:lang="en"><p>Moscow.</p></bio><xref ref-type="aff" rid="aff-6"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Филоненко</surname><given-names>Е. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Filonenko</surname><given-names>E. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва.</p></bio><bio xml:lang="en"><p>Moscow.</p></bio><xref ref-type="aff" rid="aff-6"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru">Институт общей физики им. А.М. Прохорова РАН; Национальный исследовательский ядерный университет МИФИ.<country>Россия</country></aff><aff xml:lang="en">Prokhorov General Physics Institute RAS; National research nuclear university "MEPHI".<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru">Национальный исследовательский ядерный университет МИФИ.<country>Россия</country></aff><aff xml:lang="en">National research nuclear university "MEPHI".<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru">Федеральный научно-исследовательский центр эпидемиологии и микробиологии им. почетного акад. Н.Ф. Гамалеи.<country>Россия</country></aff><aff xml:lang="en">N.F. Gamaleya Federal Research Center for Epidemiology &amp; Microbiology.<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-4"><aff xml:lang="ru">Московский технологический университет МИРЭА.<country>Россия</country></aff><aff xml:lang="en">Moscow Technological University MIREA.<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-5"><aff xml:lang="ru">Национальный исследовательский ядерный университет МИФИ.<country>Россия</country></aff><aff xml:lang="en">Prokhorov General Physics Institute RAS.<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-6"><aff xml:lang="ru">Национальный медицинский исследовательский радиологический центр Минздрава России.<country>Россия</country></aff><aff xml:lang="en">National Medical Research Radiological Centre of the Ministry of Health of the Russian  Federation.<country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2017</year></pub-date><pub-date pub-type="epub"><day>07</day><month>12</month><year>2017</year></pub-date><volume>6</volume><issue>3</issue><fpage>16</fpage><lpage>32</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Меерович Г.А., Ахлюстина Е.В., Тиганова И.Г., Панов А.В., Тюкова В.С., Толордава Э.Р., Алексеева Н.В., Линьков К.Г., Романова Ю.М., Грин М.А., Миронов А.Ф., Лощенов В.Б., Каприн А.Д., Филоненко Е.В., 2017</copyright-statement><copyright-year>2017</copyright-year><copyright-holder xml:lang="ru">Меерович Г.А., Ахлюстина Е.В., Тиганова И.Г., Панов А.В., Тюкова В.С., Толордава Э.Р., Алексеева Н.В., Линьков К.Г., Романова Ю.М., Грин М.А., Миронов А.Ф., Лощенов В.Б., Каприн А.Д., Филоненко Е.В.</copyright-holder><copyright-holder xml:lang="en">Meerovich G.A., Akhlyustina E.V., Tiganova I.G., Panov V.A., Tyukova V.S., Тolordava E.R., Alekseeva N.V., Linkov K.G., Romanova Y.M., Grin M.A., Mironov A.F., Loshchenov V.B., Kaprin A.D., Filonenko E.V.</copyright-holder><license license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.pdt-journal.com/jour/article/view/182">https://www.pdt-journal.com/jour/article/view/182</self-uri><abstract><p>Катионные бактериохлорины перспективны как антимикробные фотосенсибилизаторы для антибактериальной фотодинамической терапии. Настоящая работа посвящена изучению свойств нового наноструктурированного катионного фотосенсибилизатора на основе циклодекстриновой дисперсии производного бактериохлорина – метилового эфира 133-N-(N-метилникотинил)бактериопурпуринимида (КБХ), с целью оптимизации состава дисперсии и выбора интервала времени от введения фотосенсибилизатора до проведения фотодинамической терапии инфицированных гнойных ран. Оценены особенности поглощения и флуоресценции фотосенсибилизатора в зависимости от его концентрации и соотношения между компонентами дисперсии. Изучена фармакокинетика и биораспределение фотосенсибилизатора в органах и тканях интактных мышей и гнойных ранах, инфицированных P. аeruginosa или S. aureus. Предварительные исследования показали высокую эффективность антимикробной фотодинамической терапии инфицированных гнойных ран с циклодекстрированной дисперсией КБХ. Проведенные исследования поглощения и спектрально-флуоресцентных свойств его лекарственной формы в зависимости от ее состава позволили рекомендовать использование массового отношения КБХ : циклодекстрин около 1:200 и введение для уменьшения агрегации 0,1% Твин-80. Установлено, что КБХ быстро выводится из кровотока мыши: более 70% – за 2 ч, 95% – за 1 сут , более 99% – за 6 сут. Из кожи и мышц около 98% выводится за 6 сут. Фотосенсибилизатор накапливается и удерживается до 24 ч в печени и почках. Это позволяет предположить, что элиминирование фотосенсибилизатора из организма мышей происходит через почки и печень. Обнаружено, что в тканях, в частности, в коже и мышцах, через 24 ч наблюдается частичная агрегация фотосенсибилизатора. Это позволяет предположить, что уменьшение интенсивности его флуоресценции через 24 и более часа связано не только с его элиминацией из организма, но и с агрегацией. Спектрально-флуоресцентное исследования показали, что КБХ селективно накапливается в инфицированных ранах, флуоресцентная контрастность лежит в пределах 3–4. Наиболее высокие значения концентрации и селективности его накопления в инфицированных ранах были достигнуты через 1,5–3 ч после внутривенного введения. Облучение через 2 ч после введения обеспечило высокую эффективность терапии инфицированных гнойных ран.</p></abstract><trans-abstract xml:lang="en"><p>Cationic bacteriochlorins are promising as antibacterial photosensitizers (PS) for antibacterial photodynamic therapy. Current work is devoted to the study of properties of new nanostructured cationic photosensitizer based on cyclodextrin dispersion of bacteriochlorine derivative – 133-N-(N-methylnicotinyl)-bacteriopurpurinimide methyl ester, for optimization of dispersion composition and selection of time interval between administration of the PS and photodynamic ttherapy of infected septic wounds. Specifics of absorption and fluorescence of PS in dependence of its concentration and proportions of components in dispersion was assessed. Pharmacokinetics and biodistribution of PS were studies in vivo in organs and tissues of intact mice and septic wounds infected with P. аeruginosa or S. aureus. The preliminary studies have shown high efficiency of antimicrobial photodynamic therapy of septic wounds with cyclodextrin dispersion of 133-N-(N-methylnicotinyl)-bacteriopurpurinimide methyl ester. Results of study of absorption and spectral and fluorescence properties of its drug formulation depending on its composition allowed to recommend the use of weight ratio 133-N-(N-methylnicotinyl)bacteriopurpurinimide methyl ester : cyclodextrin about 1:200 and addition of 0,1% Tween 80 to reduce aggregation. The study showed that 133-N-(N-methylnicotinyl)-bacteriopurpurinimide methyl ester was rapidly cleared from mouse blood circulation: more than 70% – for 2 h, 95% – for 1 day, more than 99% – for 6 days. About 98% was cleared from skin and muscles for 6 days. The long-term (up to 24 h) persistence of PS were observed in liver and kidneys, however more than 99% was cleared for 6 days. Thus, it may be supposed that elimination of PS form mice body is through kidneys and liver. After 24 h partial PS aggregation in tissues, particularly in skin and muscles, was observed. Thus, it may be supposed that the reduce of fluorescence intensity after 24 hand later was associated not only with its elimination from body but with its aggregation. Spectral and fluorescence studies showed that 133-N-(Nmethylnicotinyl)-bacteriopurpurinimide methyl ester selectively accumulated in septic wounds, fluorescence contrast was in the range of 3–4. The highest values of concentration and selectivity of its accumulation were achieved at 1.5–3 h after intravenous injection. The irradiation 2 h after injection provided high efficacy of the therapy of septic wounds.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>антимикробная фотодинамическая терапия</kwd><kwd>метиловый эфир 133-N-(N-метилникотинил)бактериопурпуринимида</kwd><kwd>производные бактериохлорина</kwd><kwd>поглощение</kwd><kwd>флуоресценция</kwd><kwd>агрегация</kwd><kwd>циклодекстрин</kwd></kwd-group><kwd-group xml:lang="en"><kwd>antibacterial photodynamic therapy</kwd><kwd>133-N-(N-methylnicotinyl)-bacteriopurpurinimide methyl ester</kwd><kwd>bacteriochlorine derivative</kwd><kwd>absorption</kwd><kwd>fluorescence</kwd><kwd>aggregation</kwd><kwd>cyclodextrin</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Porphyrins as antimicrobial photosensitizing agents, in Photodynamic Inactivation of Microbial Pathogens: Medical and Environmental Applications / Eds. M.R. Hamblin and G. 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