Russian Journal of Biological Physics and Chemisrty Russian Journal of Biological Physics and Chemisrty АКТУАЛЬНЫЕ ВОПРОСЫ БИОЛОГИЧЕСКОЙ ФИЗИКИ И ХИМИИ 2499-9962 54354 Общая биофизика General biophysics Общая биофизика STUDY OF STABILITY OF LIPOSOMES LOADED WITH TETRAKIS(4-BENZYLOXYPHENYL)TETRACYANOPORPHYRAZINE ИССЛЕДОВАНИЕ СТАБИЛЬНОСТИ ЛИПОСОМ, ЗАГРУЖЕННЫХ ТЕТРАКИС(4-БЕНЗИЛОКСИФЕНИЛ)ТЕТРАЦИАНОПОРФИРАЗИНОМ Дьякова Д В Dyakova D V daryadyakova@mail.ru Лермонтова С А Lermontova S A Клапшина Л Г Klapshina L G Юдинцев А В Yudintsev A V Балалаева И В Balalaeva I V Национальный исследовательский Нижегородский государственный университет им. Н.И. Лобачевского ru Lobachevsky University ru Национальный исследовательский Нижегородский государственный университет им. Н.И. Лобачевского; Институт металлоорганической химии им. Г.А. Разуваева РАН ru Lobachevsky University; G.A. Razuvaev Institute of Organometallic Chemistry of the RAS ru Институт металлоорганической химии им. Г.А. Разуваева РАН ru G.A. Razuvaev Institute of Organometallic Chemistry of the RAS ru Национальный исследовательский Нижегородский государственный университет им. Н.И. Лобачевского ru Lobachevsky University ru Национальный исследовательский Нижегородский государственный университет им. Н.И. Лобачевского ru Lobachevsky University ru 25 12 2018 25 12 2018 3 4 718 723 20 12 2018 20 12 2018 https://rusjbpc.ru/en/nauka/article/54354/view

Фотосенсибилизаторы из группы тетра(арил)тетрацианопорфиразинов являются перспективными красителями для фотодинамической терапии опухолей и имеют уникальные свойства. Однако, применение таких фотосенсибилизаторов (ФС) in vivo требует использования специальных переносчиков, обеспечивающих эффективную доставку и селективное накопление препаратов в области злокачественного новообразования. Данное исследование направлено на изучение стабильности липосом различного состава при условии их загрузки фотосенсибилизатором тетракис(4-бензилоксифенил)тетрацианопорфиразином (Pz). Показано, что исследуемый фотосенсибилизатор с эффективностью до 33 % может загружаться в нейтральные и отрицательно заряженные липосомы, состоящие из смеси фосфатидилхолина с холестерином и фосфатидилглицеролом, соответственно, без существенного влияния на их размер. Модификация поверхности липосом путем добавления гидрофильного полимера полиэтиленгликоля (в составе фосфатидилэтаноламин-N-[карбокси(полиэтилен гликоля)-2000]) приводит к увеличению эффективности загрузки фотосенсибилизатора в 2,2-2,5 раза (до 80 %). При этом размер липосом с покрытием полиэтиленгликолем при загрузке ФС увеличивается вдвое по сравнению с везикулами без Pz, что свидетельствует об их агрегации. Высокая эффективность загрузки Pz в липосомы дает предпосылки для дальнейшего создания липосомальной формы фотосенсибилизаторов данного класса при условии изменения способа поверхностного экранирования.

Photosensitizers from the group of tetra(aryl)tetracyanoporphyrazines are the promising dyes for photodynamic therapy of tumors with unique properties. However, in vivo application of such photosensitizers (PS) requires the use of special drug carriers that ensure effective delivery and selective accumulation in the tumor site. The present study is focused on obtaining liposomes with different lipid composition loaded with tetrakis(4-benzyloxyphenyl)tetracyanoporphyrazine (Pz) and examining their stability. An efficient loading of the dye (with loading efficiency up to 33 %) was proved for the neutral and negatively charged liposomes composed of phosphatidylcholine with cholesterol and phosphatidylglycerol. It was found that porphyrazine do not affect the size of these vesicles. Surface modification of the liposomes by adding polyethylene glycol (in the composition of phosphatidylethanolamine-N-[carboxy (polyethylene glycol)-2000]) increases the loading efficiency of the photosensitizer by 2,2-2,5 times (up to 80 %). At the same time, the size of liposomes coated with polyethylene glycol is doubled after Pz loading compared to vesicles without Pz. This result indicates that Pz causes the aggregation of such liposomes. The high loading efficiency of Pz into liposomes gives the prerequisites for the further development of the liposomal form of photosensitizers of this class by means of optimization of the method of surface coating.

 порфиразин липосомы фотодинамическая терапия фотосенсибилизатор porphyrazine liposomes photodynamic therapy photosensitizer

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