vestichИзвестия Национальной академии наук Беларуси. Серия химических наукProceedings of the National Academy of Sciences of Belarus, Chemical Series1561-83312524-2342The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1561-8331-2024-60-4-300-313vestich-916Research ArticleКОЛЛОИДНАЯ ХИМИЯCOLLOIDAL CHEMISTRYПолучение, морфология, антирадикальная и биологическая активность кверцетин-содержащих наночастиц зеина и их субмикронных агрегатовPreparation, morphology, antiradical and biological activity of quercetin-containing nanoparticles of zein and their submicron aggregateshttps://orcid.org/0000-0001-6601-2707ШутоваТ. Г.ShutavaT. G.

Шутова Татьяна Геннадьевна – кандидат химических наук, доцент, ведущий научный сотрудник

ул. Ф. Скорины, 36, 220084, Минск

Shutava Tatsiana G. – Ph. D. (Chemistry), Associate Professor, Leading Researcher

36, F. Skaryna Str., 220084, Minsk

shutova@ichnm.byПотаповичА. И.PotapovichA. I.

Потапович Алла Ивановна – кандидат биологических наук, ведущий научный сотрудник

пр-т Независимости, 4, 220030

Potapovich Alla I. – Ph. D. (Biology), Leading Researcher

4, Nezavisimosti Ave., 220030, Minsk

pot-alla@rambler.ruКостюкТ. В.KostyukT. V.

Костюк Татьяна Владимировна – младший научный сотрудник

пр-т Независимости, 4, 220030

Kostyuk Tatyana V. – Junior Researcher

4, Nezavisimosti Ave., 220030, Minsk

1011@tut.byhttps://orcid.org/0000-0003-3083-3962ЛивоновичК. С.LivanovichK S.

Ливонович Константин Сергеевич – кандидат химических наук, старший научный сотрудник

ул. Ф. Скорины, 36, 220084, Минск

Livanovich Kanstantsin S. – Ph. D. (Chemistry), Senior Researcher

36, F. Skaryna Str., 220084, Minsk

kslivonovich@ichnm.byhttps://orcid.org/0000-0002-1246-4131КостюкВ. А.KostyukV. A.

Костюк Владимир Андреевич – доктор химических наук, доцент; заведующий лабораторией

пр-т Независимости, 4, 220030

Kostyuk Vladimir A. – D. Sc. (Chemistry), Associate Professor, Head of the Laboratory

4, Nezavisimosti Ave., 220030, Minsk

kostyuk@bsu.byИнститут химии новых материалов Национальной академии наук БеларусиInstitute of Chemistry of New Materials, National Academy of Sciences of BelarusБелорусский государственный университетBelarusian State University202430112024604300313Copyright © Шутова Т.Г., Потапович А.И., Костюк Т.В., Ливонович К.С., Костюк В.А., 20242024Шутова Т.Г., Потапович А.И., Костюк Т.В., Ливонович К.С., Костюк В.А.Shutava T.G., Potapovich A.I., Kostyuk T.V., Livanovich K.S., Kostyuk V.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestichem.belnauka.by/jour/article/view/916

Наночастицы проламинового белка кукурузы зеина (NPQ), содержащие 0,005–0,26 г/г кверцетина (Q), получены десольватацией 25–30 мг/мл растворов белка в этаноле, содержащих капсулируемое соединение, водным раствором полистиролсульфоната. Размеры наночастиц зеина и их агрегатов охарактеризованы методами динамического светорассеяния и атомно-силовой микроскопии, содержание кверцетина – методом Фолина–Чокальтеу. При отношении кверцетин/зеин в растворе менее 0,08 г/г полифенол количественно включается в наночастицы, а их гидродинамический диаметр равен 60–75 нм. С увеличением отношения кверцетин/зеин до 0,20 г/г средний диаметр частиц возрастает до 150 нм. В концентрированных дисперсиях образуются агрегаты диаметром порядка 500–600 нм. Изучена кинетика высвобождения кверцетина из NPQ с различной массовой долей Q в дистиллированной воде и растворах, имитирующих среду желудка и кишечника, при 37 °С. Наночастицы зеина проявляют слабую активность в реакции с катион-радикалами АБТС. Инкапсулированный в матрицу зеина Q в целом сохраняет антирадикальную активность, характерную для свободного флавоноида, однако скорость обесцвечивания катион- радикалов АБТС замедляется из-за пролонгированного высвобождения кверцетина из NPQ. Цитопротекторные свойства кверцетина в наночастицах зеина существенно снижаются и проявляются в частичном сохранении целостности клеточных мембран и уменьшении выхода лактатдегидрогеназы из УФ-С-облученных клеток НаСаТ. В отличие от свободного кверцетина введение Q в наночастицах зеина или их субмикронных агрегатов увеличивает количество метаболически мертвых УФ-С-облученных клеток НаСаТ, усиливая цитотоксическое действие УФ-излучения. Аналогичным эффектом обладают пустые зеиновые агрегаты субмикронных размеров.

Nanoparticles of corn prolamine protein zein (NPQ) containing 0.005–0.26 g/g quercetin (Q) were prepared by desolvation of a 25–30 mg/mL ethanol protein solution containing the encapsulated compound with an aqueous polystyrene sulfonate. The size of zein nanoparticles and their aggregates was characterized by dynamic light scattering and atomic force microscopy; the quercetin content – by the Folin-Ciocalteu assay. While the quercetin/zein ratio in solution is less than 0.08 g/g, the polyphenol is quantitatively included in the nanoparticles, and their hydrodynamic diameter is 60–75 nm. As the quercetin/zein ratio rises to 0.20 g/g, the average particle diameter increases to 150 nm. In concentrated dispersions, aggregates with a diameter of 500–600 nm are formed. The kinetics of quercetin release from NPQ with different mass fractions of Q in distilled water and solutions simulating the environment of the stomach and intestines at 37 °C were studied.

Zein nanoparticles exhibit weak activity in the reaction with ABTS cation-radicals. Quercetin encapsulated in the zein matrix generally retains the antiradical activity characteristic of the free flavonoid, however, the rate of decolorization of ABTS cation-radicals decreases due to the prolonged release of quercetin from NPQ. The cytoprotective properties of quercetin in zein nanoparticles are significantly reduced and manifest themselves only in partial preservation of the integrity of cell membranes and a decrease in the release of lactate dehydrogenase from UV-C irradiated HaCaT cells. In contrast to free quercetin, the introduction of Q in zein nanoparticles or their submicron aggregates increases the number of metabolically dead UV-C-irradiated HaCaT cells, enhancing the cytotoxic effect of UV radiation. Empty zein aggregates of submicron size have a similar effect.

зеинкверцетиннаночастицыантирадикальная активностьцитотоксичностьцитопротекторные свойстваzeinquercetinnanoparticlesantiradical activitycytotoxicitycytoprotective propertiesReferencesPolyphenols and their nanoformulations: protective effects against human diseases / S. Anand [et al.] // Life. – 2022. – Vol. 12, № 10. – P. 1639. https://doi.org/10.3390/life12101639Anand S., Sowbhagya R., Ansari M. A., Alzohairy M. A., Alomary M. N., Almalik A. I., Ahmad W., Tripathi T., Elderdery A. Y. Polyphenols and their nanoformulations: protective effects against human diseases. Life, 2022, vol. 12, no. 10, p. 1639. https://doi.org/10.3390/life12101639Цитопротекторный потенциал полифенольных экстрактов плодов рода Vaccinium, произрастающих на террирории Югры, в условиях in vitro / Е. А. Белова [и др.] // Вестн. СурГУ. Медицина. – 2020. – Т. 43, № 1. – С. 86–93. https://doi.org/10.34822/2304-9448-2020-1-86-93Belova E. A., Krivykh E. A., Kavushevskaya N. S., Bystrevskaya L. K., Zhautikova S. B. Cytoprotective potential in polyphenolic extracts of vaccinium fruits in the Ugra territory in vitro. Vestnik SurGU. Meditsina = Bulletin of Surgut State University. Medicine, 2020, vol. 43, no. 1, pp. 86–93 (in Russian). https://doi.org/10.34822/2304-9448-2020-1-86-93Encapsulation of quercetin in biopolymer-coated zein nanoparticles: formation, stability, antioxidant capacity, and bioaccessibility / Y. Zou [et al.] // Food Hydrocoll. – 2021. – Vol. 120, № 2. – P. 106980. https://doi.org/10.1016/j.foodhyd.2021.106980Zou Y., Qian Y., Rong X., Cao K., McClements D. J., Hu K. Encapsulation of quercetin in biopolymer-coated zein nanoparticles: formation, stability, antioxidant capacity, and bioaccessibility. Food Hydrocolloids, 2021, vol. 120, no. 2, pp. 106980. https://doi.org/10.1016/j.foodhyd.2021.106980Natural substances for prevention of skin photoaging: screening systems in the development of sunscreen and rejuvenation cosmetics / V. Kostyuk [et al.] // Rejuvenation Res. – 2018. – Vol. 21, №2. – P. 91–101. https://doi.org/10.1089/rej.2017.1931Kostyuk V., Potapovich A., Albuhaydar A. R., Mayer W., De Luca C., Korkina L. Natural substances for prevention of skin photoaging: screening systems in the development of sunscreen and rejuvenation cosmetics. Rejuvenation Research, 2018, vol. 21, no. 2, pp. 91–101. https://doi.org/10.1089/rej.2017.1931Role of the encapsulation in bioavailability of phenolic compounds / J. Grgić [et al.] // Antioxidants. – 2020. – Vol. 9, № 10. – P. 923. https://doi.org/10.3390/antiox9100923Grgić J., Šelo G., Planinić M., Tišma M., Bucić-Kojić A. Role of the encapsulation in bioavailability of phenolic compounds. Antioxidants, 2020, vol. 9, no. 10, pp. 923. https://doi.org/10.3390/antiox9100923Effects of native and particulate polyphenols on DNA damage and cell viability after UV-C exposure / A. I. Potapovich [et al.] // Naunyn Schmiedebergs Arch. Pharmacol. – 2023. – Vol. 396, №. 9. – P. 1923–1930. https://doi.org/10.1007/s00210023-02443-3Potapovich A. I., Kostyuk T. V., Ishutina O. V., Shutava T. G., Kostyuk V. A. Effects of native and particulate polyphenols on DNA damage and cell viability after UV-C exposure. Naunyn-Schmiedeberg’s archives of pharmacology, 2023, vol. 396, no. 9, pp. 1923–1930. https://doi.org/10.1007/s00210-023-02443-3Parris, N. Extraction and solubility characteristics of zein proteins from dry-milled corn / N. Parris, L. C. Dickey // J. Agric. Food Chem. – 2001. – Vol. 49, № 8. – Р. 3757–3760. https://doi.org/10.1021/jf0011790Parris N., Dickey L. C. Extraction and solubility characteristics of zein proteins from dry-milled corn. Journal of agricultural and food chemistry, 2001, vol. 49, no. 8, pp. 3757–3760. https://doi.org/10.1021/jf0011790Lawton, J. W. Zein: a history of processing and use / J. W. Lawton // Cereal Chem. – 2002. – Vol. 79, № 1. – Р. 1–18. https://doi.org/10.1094/CCHEM.2002.79.1.1Lawton J. W. Zein: a history of processing and use. Cereal Chemistry, 2002, vol. 79, no. 1, pp. 1–18. https://doi.org/10.1094/CCHEM.2002.79.1.1Recent advances in food-packing, pharmaceutical and biomedical applications of zein and zein-based materials / E. Corradini [et al.] // Int. J. Mol. Sci. – 2014. – Vol. 15, № 12. – Р. 22438–22470. https://doi.org/10.3390/ijms151222438Corradini E., Curti P.S., Meniqueti A. B., Martins A. F., Rubira A. F., Muniz E. C. Recent advances in food-packing, pharmaceutical and biomedical applications of zein and zein-based materials. International journal of molecular science, 2014, vol. 15, no. 12, pp. 22438–22470. https://doi.org/10.3390/ijms151222438Pascoli, M. Zein nanoparticles and strategies to improve colloidal stability: a mini-review / M. Pascoli, R. de Lima, L.F. Fraceto // Front. Chem. – 2018. – Vol. 6. – P. 6. https://doi.org/10.3389/fchem.2018.00006Pascoli M., de Lima R., Fraceto L. F. Zein nanoparticles and strategies to improve colloidal stability: f mini-review. Frontiers in Chemistry, 2018, vol. 6, pp. 6. https://doi.org/10.3389/fchem.2018.00006Physicochemical properties and bioavailability comparison of two quercetin loading zein nanoparticles with outer shell of caseinate and chitosan / J.-F. Zhou [et al.] // Food Hydrocoll. – 2021. – Vol. 120. – P. 106959. https://doi.org/10.1016/j.foodhyd.2021.106959Zhou J.-F., Zheng G.-D., Wang W.-J., Yin Z.-P., Chen J.-G., Li J.-E., Zhang Q.-F. Physicochemical properties and bioavailability comparison of two quercetin loading zein nanoparticles with outer shell of caseinate and chitosan. Food Hydrocolloids, 2021, vol. 120, pp. 106959. https://doi.org/10.1016/j.foodhyd.2021.106959Encapsulation of quercetin in biopolymer-coated zein nanoparticles: Formation, stability, antioxidant capacity, and bioaccessibility / Y. Zou [et al.] // Food Hydrocoll. – 2021. – Vol. 120. – P. 106980. https://doi.org/10.1016/j.foodhyd.2021.106980Zou Y., Qian Y., Rong X., Cao K., McClements D. J., Hu K. Encapsulation of quercetin in biopolymer-coated zein nanoparticles: formation, stability, antioxidant capacity, and bioaccessibility. Food Hydrocolloids, 2021, vol. 120, pp. 106980. https://doi.org/10.1016/j.foodhyd.2021.106980Zein-pectin composite nanoparticles as an efficient hyperoside delivery system: fabrication, characterization, and in vitro release property / X. Wang [et al.] // LWT – Food Sci. Technol. – 2020. – Vol. 133. – P. 109869. https://doi.org/10.1016/j.lwt.2020.109869Wang X., Peng F., Liu F., Xiao Y., Li F., Lei H., Wang J., Li M., Xu H. Zein-pectin composite nanoparticles as an efficient hyperoside delivery system: fabrication, characterization, and in vitro release property. LWT – Food Science and Technology, 2020, vol. 133, pp. 109869. https://doi.org/10.1016/j.lwt.2020.109869Carriers based on zein-dextran sulfate sodium binary complex for the sustained delivery of quercetin / T. Wang [et al.] // Front. Chem. – 2020. – Vol. 8. – P. 662. https://doi.org/10.3389/fchem.2020.00662Wang T., Li X., Chen L., Li L., Janaswamy S. Carriers based on zein-dextran sulfate sodium binary complex for the sustained delivery of quercetin. Frontiers in Chemistry, 2020, vol. 8, pp. 662. https://doi.org/10.3389/fchem.2020.00662In vitro antioxidant and antitumor study of zein/SHA nanoparticles loaded with resveratrol / Q. Shi [et al.] // Food Sci. Nutr. – 2021. – Vol. 9, № 7. – P. 3530–3537. https://doi.org/10.1002/fsn3.2302Shi Q., Wang X., Tang X., Zhen N., Wang Y., Lu Z., Zhang H., Liu J., Zhou D., Huang K. In vitro antioxidant and antitumor study of zein/SHA nanoparticles loaded with resveratrol. Food Science & Nutrition, 2021, vol. 9, no. 7, pp. 3530–3537. https://doi.org/10.1002/fsn3.2302Synthesis of novel biodegradable methoxy poly(ethylene glycol)−zein micelles for effective delivery of curcumin / S. Podaralla [et al.] // Mol. Pharm. – 2012. – Vol. 9, № 9. – P. 2778−2786. https://doi.org/10.1021/mp2006455Podaralla S., Averineni R., Alqahtani M., Perumal O. Synthesis of novel biodegradable methoxy poly(ethylene glycol)−zein micelles for effective delivery of curcumin. Molecular Pharmaceutics, 2012, vol. 9, no. 9, pp. 2778−2786. https://doi.org/10.1021/mp2006455Preparation and characterization of quercetin-loaded zein nanoparticles by electrospraying and study of in vitro bioavailability / F. Rodríguez-Félix [et al.] // J. Food Sci. – 2019. – Vol. 84, № 10. – P. 2883–2897. https://doi.org/10.1111/17503841.14803Rodríguez-Félix F., Del-Toro-Sánchez C. L., Cinco-Moroyoqui F. J., Juárez J., Ruiz-Cruz S., López-Ahumada G. A., Carvajal-Millan E., Castro-Enríquez D. D., Barreras-Urbina C. G., Tapia-Hernández J. A. Preparation and characterization of quercetin-loaded zein nanoparticles by electrospraying and study of in vitro bioavailability. Journal of Food Science, 2019, vol. 84, no. 10, pp. 2883–2897. https://doi.org/10.1111/1750-3841.14803Quercetin loaded biopolymeric colloidal particles prepared by simultaneous precipitation of quercetin with hydrophobic protein in aqueous medium / A. R. Patel [et al.] // Food Chem. – 2012. – Vol. 133, № 2. – Р. 423–429. https://doi.org/10.1016/j.foodchem.2012.01.054Patel A. R., Heussen P. C. M., Hazekamp J., Drost E., Velikov, K. P. Quercetin loaded biopolymeric colloidal particles prepared by simultaneous precipitation of quercetin with hydrophobic protein in aqueous medium. Food Chemistry, 2012, vol. 133, no. 2, pp. 423–429. https://doi.org/10.1016/j.foodchem.2012.01.054Zein nanoparticles as low-cost, safe, and effective carriers to improve the oral bioavailability of resveratrol / R. Nunes [et al.] // Drug Deliv. Transl. Res. – 2020. – Vol. 10, № 3. – P. 826–837. https://doi.org/10.1007/s13346-020-00738-zNunes R., Baião A., Monteiro D., das Neves J., Sarmento B. Zein nanoparticles as low-cost, safe, and effective carriers to improve the oral bioavailability of resveratrol. Drug delivery and translational research, 2020, vol. 10, no. 3, pp. 826–837. https://doi.org/10.1007/s13346-020-00738-zZeinvs PLGA-based nanoparticles containing rutin: a comparative investigation / A. Gagliardi [et al.] // Mater. Sci. Eng. C. – 2021. – Vol. 118. – P. 111538. https://doi.org/10.1016/j.msec.2020.111538Gagliardi A., Paolino D., Costa N., Fresta M., Cosco D. Zeinvs PLGA-based nanoparticles containing rutin: A comparative investigation. Materials Science & Engineering C, 2021, vol. 118, pp. 111538. https://doi.org/10.1016/j.msec.2020.111538Paclitaxel-loaded sodium deoxycholate-stabilized zein nanoparticles: characterization and in vitro cytotoxicity / A. Gagliardi [et al.] // Heliyon. – 2019. – Vol. 5. – P. e02422. https://doi.org/10.1016/j.heliyon.2019.e02422Gagliardi A., Bonacci S., Paolino D., Celia C., Procopio A., Fresta M., Cosco D. Paclitaxel-loaded sodium deoxycholate-stabilized zein nanoparticles: characterization and in vitro cytotoxicity. Heliyon, 2019, vol. 5, pp. e02422. https://doi.org/10.1016/j.heliyon.2019.e02422Encapsulation of lovastatin in zein nanoparticles exhibits enhanced apoptotic activity in HepG2 cells / N. A. Alhakamy [et al.] // Int. J. Mol. Sci. – 2019. – Vol. 20. – P. 5788. https://doi.org/10.3390/ijms20225788Alhakamy N. A., Ahmed O. A. A., Aldawsari H. M., Alfaifi M. Y., Eid B. G., Abdel-Naim A. B., Fahmy U. A. Encapsulation of Lovastatin in Zein Nanoparticles Exhibits Enhanced Apoptotic Activity in HepG2 Cells. International journal of molecular science, 2019, vol. 20, pp. 5788. https://doi.org/10.3390/ijms20225788Lecithins-zein nanoparticles for antifungal treatment: enhancement and prolongation of drug retention in skin with reduced toxicity / S. Zhang [et al.] // Int. J. Pharm. – 2020. – Vol. 590. – P. 119894. https://doi.org/10.1016/j.ijpharm.2020.119894Zhang S., Song W., Wu H., Wang J., Wang Y., Zhang Z., Lv H. Lecithins-Zein nanoparticles for antifungal treatment: Enhancement and prolongation of drug retention in skin with reduced toxicity. International Journal of Pharmaceutics, 2020, vol. 590, pp. 119894. https://doi.org/10.1016/j.ijpharm.2020.119894Zein nanoparticles as eco-friendly carrier systems for botanical repellents aiming sustainable agriculture / J. L. de Oliveira [et al.] // J. Agric. Food Chem. – 2018. – Vol. 66, № 6. – P. 1330−1340. https://doi.org/10.1021/acs.jafc.7b05552de Oliveira J. L., Campos E. V. R., Pereira A. E. S., Pasquoto T., Lima R., Grillo R., de Andrade D. J., dos Santos F. A., Fraceto L. F. Zein Nanoparticles as Eco-Friendly Carrier Systems for Botanical Repellents Aiming Sustainable Agriculture. Journal of Agricultural and Food Chemistry, 2018, vol. 66, no. 6, pp. 1330−1340. https://doi.org/10.1021/acs.jafc.7b05552Nakamura, Y. Method for analysis of tannic acid and its metabolites in biological samples: application to tannic acid metabolism in the rat / Y. Nakamura, S. Tsuji, Y. Tonogai // J. Agric. Food Chem. – 2003. – Vol. 51, № 1. – P. 331–334. https:// doi.org/10.1021/jf020847+Nakamura Y., Tsuji S., Tonogai Y. Method for Analysis of Tannic Acid and Its Metabolites in Biological Samples: Application to Tannic Acid Metabolism in the Rat. Journal of Agricultural and Food Chemistry, 2003, vol. 51, no. 1, pp. 331–334. https://doi.org/10.1021/jf020847+Antioxidant activity applying an improved ABTS radical cation decolorization assay / R. Re [et al.] // Free Radical Biol. Med. – 1999. – Vol. 26, № 9–10. – P. 1231–1237. https://doi.org/10.1016/S0891-5849(98)00315-3Re R., Pellegrini A., Proteggente A., Pannala A., Yang M., Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radical Biology and Medicine, 1999, vol. 26, no. 9–10, pp. 1231–1237. https://doi.org/10.1016/S0891-5849(98)00315-3Singh, B. R. Basic aspects of the technique and applications of infrared spectroscopy of peptides and proteins in infrared analysis of peptides and proteins / B. R. Singh // ACS Sym. Ser. – 2000. – Vol. 750. – P. 2–37. https://doi.org/10.1021/bk-2000-0750.ch001Singh B. R. Basic Aspects of the Technique and Applications of Infrared Spectroscopy of Peptides and Proteins in Infrared Analysis of Peptides and Proteins. ACS Symposium Series, 2000, vol. 750, pp. 2–37. https://doi.org/10.1021/bk2000-0750.ch001Zein nanoparticle as a novel BMP6 derived peptide carrier for enhanced osteogenic differentiation of C2C12 cells / M. Hadavi [et al.] // Artif. Cells Nanomed. Biotechnol. – 2018. – Vol. 46, № 1. – Р. 559–567. https://doi.org/10.1080/21691401.2018.143164Hadavi M., Hasannia S., Faghihi S., Mashayekhi F., Homazadeh H., Mostofi S. B. Zein nanoparticle as a novel BMP6 derived peptide carrier for enhanced osteogenic differentiation of C2C12 cells. Artificial Cells, Nanomedicine, and Biotechnology, 2018, vol. 46, no. 1, pp. 559–567. https://doi.org/10.1080/21691401.2018.143164Colorful polyelectrolytes: an atom transfer radical polymerization route to fluorescent polystyrene sulfonate / W. Huberty [et al.] // J. Fluoresc. – 2016. – Vol. 26. – P. 609–615. https://doi.org/10.1007/s10895-015-1747-2Huberty W., Tong X., Balamurugan S., Deville K., Russo P. S., Zhang D. Colorful polyelectrolytes: an atom transfer radical polymerization route to fluorescent polystyrene sulfonate. Journal of Fluorescence, 2016, vol. 26, pp. 609–615. https:// doi.org/10.1007/s10895-015-1747-2Infrared spectrum analysis of some flavonoids / M. Heneczkowski [et al.] // Acta Pol. Pharm. – 2001. – Vol. 58, № 6. – P. 415–420. PMID: 12197612Heneczkowski M., Kopacz M., Nowak D., Kuzniar A. Infrared spectrum analysis of some flavonoids. Acta Poloniae Pharmaceutica, 2001, vol. 58, no. 6, pp. 415–420. PMID: 12197612Pohjala, L. Aggregating behavior of phenolic compounds – a source of false bioassay results / L. Pohjala, P. Tammela // Molecules. – 2012. – Vol. 17, № 9. – P. 10774–10790. https://doi.org/10.3390/molecules170910774Pohjala L., Tammela P. Aggregating behavior of phenolic compounds — a source of false bioassay results. Molecules, 2012, vol. 17, no. 9, pp. 10774–10790. https://doi.org/10.3390/molecules170910774Multiple interactions between polyphenols and a salivary proline-rich protein repeat result in complexation and precipitation / N. J. Baxter [et al.] // Biochem. – 1997. – Vol. 36, № 18. – P. 5566–5577. https://doi.org/10.1021/bi9700328Baxter N. J., Lilley T. H., Haslam E., Williamson M. P. Multiple interactions between polyphenols and a salivary proline-rich protein repeat result in complexation and precipitation. Biochemistry, 1997, vol. 36, no. 18, pp. 5566–5577. https://doi.org/10.1021/bi9700328Identification of the products of oxidation of quercetin by air oxygen at ambient temperature / I G. Zenkevich [et al.] // Molecules. – 2007. – Vol. 12, № 3. – Р. 654–72. https://doi.org/10.3390/12030654Zenkevich I. G., Eshchenko A. Y., Makarova S. V., Vitenberg A. G., Dobryakov Y. G., Utsal V. A. Identification of the products of oxidation of quercetin by air oxygen at ambient temperature. Molecules, 2007, vol. 12, no. 3, pp. 654–72. https://doi.org/10.3390/12030654Chebotarev, A. N. Study of the AcidBase Properties of Quercetin in Aqueous Solutions by Color Measurements / A. N. Chebotarev, D. V. Snigur // J. Anal. Chem. – 2015. – Vol. 70, № 1. – Р. 55–59. https://doi.org/10.1134/S1061934815010062Chebotarev A. N., Snigur D. V. Study of the AcidBase Properties of Quercetin in Aqueous Solutions by Color Measurements. Journal Analytical Chemistry, 2015, vol. 70, no. 1, pp. 55–59. https://doi.org/10.1134/S1061934815010062Relation between Droplet Size Distributions and Physical Stability for Zein Microfluidized Emulsions / J. Santos [et al.] // Polymers. – 2022. – Vol. 14, № 11. – P. 2195. https://doi.org/10.3390/polym14112195Santos J., Trujillo-Cayado L. A.; Carrillo F., López-Castejón M. L., Alfaro-Rodríguez M. C. Relation between Droplet Size Distributions and Physical Stability for Zein Microfluidized Emulsions. Polymers, 2022, vol. 14, no. 11, pp. 2195. https:// doi.org/10.3390/polym14112195The effect of pH and cocrystal quercetin-isonicotinamide on quercetin solubility and its thermodynamic / B. Wisudyaningsih [et al.] // Res. J. Pharm. Technol. – 2021. – Vol. 14, № 9. – P. 4657–4661. https://doi.org/10.52711/0974360X.2021.00809Wisudyaningsih B., Sallama S., Siswodihardjo S., Setyawan D. The Effect of pH and Cocrystal Quercetin-Isonicotinamide on Quercetin Solubility and its Thermodynamic. Research Journal of Pharmacy and Technology, 2021, vol. 14, no. 9, pp. 4657–4661. https://doi.org/10.52711/0974-360X.2021.00809Shape dependent cytotoxicity of PLGA-PEG nanoparticles on human cells / B. Zhang [et al.] // Sci. Rep. – 2017. – Vol. 7. – P. 7315. https://doi.org/10.1038/s41598-017-07588-9Zhang B., Lung P. S., Zhao S., Chu Z., Chrzanowski W., Li Q. Shape dependent cytotoxicity of PLGA-PEG nanoparticles on human cells. Scientific Reports, 2017, vol. 7, pp. 7315. https://doi.org/10.1038/s41598-017-07588-9Effect of secondary particle size of nickel oxide on nanoparticles on cytotoxicity in A549 cells / T. Kawakami [et al.] // J. Toxicol. Sci. – 2022. – Vol. 47, № 4. – P. 151–157. https://doi.org/10.2131/jts.47.151Kawakami T., Miyajima A., Komoriya K., Kato R., Isama K. Effect of secondary particle size of nickel oxide on nanoparticles on cytotoxicity in A549 cells. Journal of Toxicological Sciences, 2022, vol. 47, no. 4, pp. 151–157. https://doi.org/10.2131/jts.47.151Soto, K. Cytotoxic effects of aggregated nanomaterials / K. Soto, K. M. Garza, L. E. Murr // Acta Biomater. – 2007. – Vol. 3, № 3. – P. 351–358. https://doi.org.10.1016/j.actbio.2006.11.004Soto K., Garza K. M., Murr L. E. Cytotoxic effects of aggregated nanomaterials. Acta Biomaterialia, 2007, vol. 3, no. 3, pp. 351–358. https://doi.org/10.1016/j.actbio.2006.11.004Plant polyphenols against UV-C-induced cellular death / V. Kostyuk [et al.] // Planta Med. – 2008. – Vol. 74, № 5. – P. 509–517. https://doi.org/10.1055/s-2008-1074499Kostyuk V., Potapovich A., Suhan T., De Luca C., Pressi G., Dal Toso R., Korkina L. Plant polyphenols against UV-C-induced cellular death. Planta medica. 2008, vol. 74, no. 5, pp. 509–514. https://doi.org/10.1055/s-2008-1074499

The authors declare that there are no conflicts of interest present.