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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">pharmjournal</journal-id><journal-title-group><journal-title xml:lang="ru">Разработка и регистрация лекарственных средств</journal-title><trans-title-group xml:lang="en"><trans-title>Drug development &amp; registration</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2305-2066</issn><issn pub-type="epub">2658-5049</issn><publisher><publisher-name>LLC «CPHA»</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.33380/2305-2066-2019-8-2-16-21</article-id><article-id custom-type="elpub" pub-id-type="custom">pharmjournal-676</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>ПОИСК И РАЗРАБОТКА НОВЫХ ЛЕКАРСТВЕННЫХ СРЕДСТВ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>RESEARCH AND DEVELOPMENT OF NEW DRUG PRODUCTS</subject></subj-group></article-categories><title-group><article-title>Изучение десорбции и высвобождения терпено-индольных алкалоидов винкристина и винбластина из эритроцитарных клеточных носителей</article-title><trans-title-group xml:lang="en"><trans-title>Study of Desorbtion and Exemption of Terpeno-indole Alkaloids of Vinkristin and Vinblastin from Erythrocitary Cell Carriers</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>Тринеева</surname><given-names>О. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Trineeva</surname><given-names>O. V.</given-names></name></name-alternatives><email xlink:type="simple">trineevaov@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>Халахакун</surname><given-names>А. Д.</given-names></name><name name-style="western" xml:lang="en"><surname>Khalahakun</surname><given-names>A. D.</given-names></name></name-alternatives><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБОУ ВО «Воронежский государственный университет»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Voronezh State University</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2019</year></pub-date><pub-date pub-type="epub"><day>29</day><month>05</month><year>2019</year></pub-date><volume>8</volume><issue>2</issue><fpage>16</fpage><lpage>21</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Тринеева О.В., Халахакун А.Д., 2019</copyright-statement><copyright-year>2019</copyright-year><copyright-holder xml:lang="ru">Тринеева О.В., Халахакун А.Д.</copyright-holder><copyright-holder xml:lang="en">Trineeva O.V., Khalahakun A.D.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" 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.pharmjournal.ru/jour/article/view/676">https://www.pharmjournal.ru/jour/article/view/676</self-uri><abstract><sec><title>Введение</title><p>Введение. Сотрудниками кафедры фармацевтической химии и фармацевтической технологии были получены модифицированные формы известных в терапии онкологических заболеваний терпено-индольных алкалоидов (ТИА) – винкристина (VCR) и винбластина (VBL) путем их включения в эритроцитарные носители (ЭН) модифицированным методом гипоосмотического лизиса в модифицированной (апротонный растворитель – диметилсульфоксид (ДМСО) и полиэтиленгликоль (ПЭГ 4000) и немодифицированной средах.</p></sec><sec><title>Цель</title><p>Цель. Целью работы являлось изучение десорбции и высвобождения ТИА – VCR и VBL из ранее полученных клеточных ЭН.</p></sec><sec><title>Материалы и методы</title><p>Материалы и методы. В проведенном эксперименте определены характеристики высвобождения инкапсулированных препаратов из эритроцитов. Установлено, что в течение 6 ч in vitro высвобождается ТИА-препаратов из эритроцитарной формы: VCR – 54,5305%, VCR : ПЭГ-4000 (1:5) – 53,3305%, VCR : PEG-4000 (1:10) – 40,1283%, VCR : ПЭГ-4000 (1:20) – 39,9869%, VCR : ДМСО (2 мг/мл) – 54,2354%, VBL – 68,0656%; VBL : PEG-4000 (1:10) – 63,8941%; VBL : PEG-4000 (1:20) – 60,7455%; VBL : PEG-400 (1:20) – 60,3529%; VBL : ДМСО (2 мг/мл) – 64,5006%. Скорость высвобождения из эритроцитарной формы, инкапсулированной в среде, модифицированной ДМСО, значительно выше, чем инкапсулированных в немодифицированной среде. Средняя скорость высвобождения ТИА из эритроцитарных форм, инкапсулированных в среде ПЭГ приблизительно одинакова.</p></sec><sec><title>Результаты и обсуждение</title><p>Результаты и обсуждение. Полученные результаты показывают, что высвобождение гемоглобина из ТИА инкапсулированных эритроцитов по сравнению с неинкапсулированными ЭН невелико. Полученные результаты показывают, что из ТИА инкапсулированных ЭН, в среднем, высвобождается 8,242±0,3135% гемоглобина по сравнению с контрольными эритроцитами – 7,53% после 6 ч инкубирования при 37 °С. Выделения же гемоглобина из ТИА инкапсулированных эритроцитов в модифицированных средах меньше, чем инкапсулированных в немодифицированной среде.</p></sec><sec><title>Заключение</title><p>Заключение. На основе этих результатов можно сделать предложение, что ПЭГ может связываться с эритроцитарной мембраной и стабилизировать ее.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Introduction</title><p>Introduction. Employees of the Department of Pharmaceutical Chemistry and Pharmaceutical Technology have obtained modified forms of terpino-indole alkaloids (ТIA) and vinbristine (VCR) and vinblastine (VBL) known in the treatment of cancer diseases by incorporating them into the erythrocyte carriers (EN) by the modified method of hypoosmotic lysis in the modified (aprotic solvent dimethyl sulfoxide (DMSO) and polyethylene glycol (PEG 4000) and unmodified media.</p></sec><sec><title>Aim</title><p>Aim. The aim of the work was to study the desorption and release of terpene-indole vincristine and vinblastine alkaloids from previously obtained cellular erythrocyte carriers.</p></sec><sec><title>Materials and methods</title><p>Materials and methods. In the experiment performed, the release characteristics of encapsulated preparations from erythrocytes were determined. TIA preparations were released from erythrocyte form in 6 hours: VCR – 54.5305%, VCR : PEG-4000 (1:5) – 53.3305%, VCR : PEG-4000 (1:10) – 40.1283%, VCR : PEG-4000 (1:20) – 39.9869%, VCR : DMSO (2 mg/ml) – 54.2354%, VBL – 68.0656%; VBL : PEG-4000 (1:10) – 63.8941%; VBL : PEG-4000 (1:20) – 60.7455%; VBL : PEG-400 (1:20) – 60.3529%; VBL : DMSO (2 mg/ml) – 64.5006%. The rate of release from an erythrocyte form encapsulated in a medium modified with DMSO is significantly higher than that encapsulated in an unmodified medium. The average rate of TIA release from erythrocyte forms encapsulated in PEG medium is approximately the same.</p></sec><sec><title>Results and discussion</title><p>Results and discussion. The results show that the release of hemoglobin from TIA encapsulated erythrocytes compared with non-encapsulated EN is small. The results show that, on average, 8.242 ± 0.3135% of hemoglobin is released from TIA encapsulated with EN, compared to control erythrocytes – 7.53% after 6 h of incubation at 37 °C. The release of hemoglobin from the TIA of encapsulated erythrocytes in modified media is less than that encapsulated in unmodified medium.</p></sec><sec><title>Conclusion</title><p>Conclusion. Based on these results, it can be suggested that PEG can bind to the erythrocyte membrane and stabilize it.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>винкристин</kwd><kwd>винбластин</kwd><kwd>клеточные формы противоопухолевых препаратов</kwd><kwd>адресные системы доставки лекарственных веществ</kwd></kwd-group><kwd-group xml:lang="en"><kwd>vincristine</kwd><kwd>vinblastine</kwd><kwd>cellular forms of antitumor drugs</kwd><kwd>targeted drug delivery systems</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">Тринеева О. В. и др. Морфологические и физико-химические свойства эритроцитарных носителей, инкапсулированных терпеноиндольными алкалоидами. Разработка и регистрация лекарственных средств. 2018; 1(22): 40–44.</mixed-citation><mixed-citation xml:lang="en">Trineeva O. V. et al. Morphological and physicochemical properties of erythrocyte carriers encapsulated with terpene-indole alkaloids. Drug development &amp; registration. 2018; 1(22): 40–44 (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Заборовский А. В., Гуревич К. Г. Моделирование направленного транспорта лекарственных веществ. Часть I. Однократное ведение. Сибирский онкологический журнал. 2017; 1(16): 59–65.</mixed-citation><mixed-citation xml:lang="en">Zaborovsky A. V., Gurevich K. G. Modeling of the directed transport of medicinal substances. Part I. Single management. Siberian Oncology Journal. 2017; 1(16): 59–65 (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Заборовский А. В., Гуревич К. Г. Моделирование направленного транспорта лекарственных веществ. Часть II. Многократное введение. Сибирский онкологический журнал. 2017; 2(16): 36–41.</mixed-citation><mixed-citation xml:lang="en">Zaborovsky A. V., Gurevich K. G. Modeling of the directed transport of medicinal substances. Part II. Repeated introduction. Siberian Oncology Journal. 2017; 2(16): 36–41 (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Ксейко Д. А., Генинг Т. П. Эффективность использования аутологичных клеток крови для адресной доставки в печень аскорбиновой кислоты с целью оптимизации коллоидно-осмотического давления крови после кровопотери. Ульяновский медико-биологический журнал. 2014; 2: 67–72.</mixed-citation><mixed-citation xml:lang="en">Kseiko D. A., Gening T. P. Efficiency of using autologous blood cells for targeted delivery of ascorbic acid to the liver in order to optimize the colloid osmotic pressure of blood after blood loss. Ulyanovsk Biomedical Journal. 2014; 2: 67–72 (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Левин Г. Я., Соснина Л. Н. Использование ультрафиолетового облучения эритроцитов для увеличения их способности депонировать лекарственные препараты. Медицинский альмонах. 2013; 3(27): 67–69.</mixed-citation><mixed-citation xml:lang="en">Levin G. Ya., Sosnina L. N. The use of ultraviolet irradiation of erythrocytes to increase their ability to deposit drugs. Medical Almonas. 2013; 3(27): 67–69 (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Левин Г. Я., Соснина Л. Н. Исследование реологических свойств эритроцитов, модифицированных для направленного транспорта лекарственных веществ. Фундаментальные исследования. 2013; 2(1): 105-109.</mixed-citation><mixed-citation xml:lang="en">Levin G. Ya., Sosnina L.N. Investigation of the rheological properties of erythrocytes modified for the directed transport of drugs. Basic research. 2013; 2(1): 105–109 (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Ивонин А. Г. и др. Направленный транспорт лекарственных препаратов: современное состояние вопроса и перспективы. Известия Коми научного центра УрО РАН. 2012; 1 (9).</mixed-citation><mixed-citation xml:lang="en">Ivonin A.G. and others. Directed transport of drugs: current state of the issue and prospects. Proceedings of the Komi Scientific Center UB RAS. 2012; 1(9) (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Banskota S. et al. Cell-Based Biohybrid Drug Delivery Systems: The Best of the Synthetic and Natural Worlds. 2017; 17(1).</mixed-citation><mixed-citation xml:lang="en">Banskota S. et al. Cell-Based Biohybrid Drug Delivery Systems: The Best of the Synthetic and Natural Worlds. 2017; 17(1).</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Bourgeaux V. et al. Drug-loaded erythrocytes: on the road toward marketing approval. Drug design, development and therapy. 2016; 10: 665–676.</mixed-citation><mixed-citation xml:lang="en">Bourgeaux V. et al. Drug-loaded erythrocytes: on the road toward marketing approval. Drug design, development and therapy. 2016; 10: 665–676.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Coker S. A. et al. A Study of the Pharmacokinetic Properties and the In Vivo Kinetics of Erythrocytes Loaded With Dexamethasone Sodium Phosphate in Healthy Volunteers. Transfusion Medicine Reviews. 2017. https://doi.org/10.1016/j.tmrv.2017.09.001</mixed-citation><mixed-citation xml:lang="en">Coker S. A. et al. A Study of the Pharmacokinetic Properties and the In Vivo Kinetics of Erythrocytes Loaded With Dexamethasone Sodium Phosphate in Healthy Volunteers. Transfusion Medicine Reviews. 2017. DOI: https://doi.org/10.1016/j.tmrv.2017.09.001</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Deloach J. et al. Effect of glutaraldehyde treatment on enzyme-loaded erythrocytes. Biochimica et Biophysica Acta (BBA) – General Subjects. 1977; 496(2): 507–515.</mixed-citation><mixed-citation xml:lang="en">Deloach J. et al. Effect of glutaraldehyde treatment on enzyme-loaded erythrocytes. Biochimica et Biophysica Acta (BBA) – General Subjects. 1977; 496(2): 507–515.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Sun Y. et al. Advances of blood cell-based drug delivery systems. European Journal of Pharmaceutical Sciences. 2017; 96: 115–128.</mixed-citation><mixed-citation xml:lang="en">Sun Y. et al. Advances of blood cell-based drug delivery systems. European Journal of Pharmaceutical Sciences. 2017; 96: 115–128.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Zocchi E. et al. Encapsulation of doxorubicin in liver-targeted erythrocytes increases the therapeutic index of the drug in a murine metastatic model. Proceedings of the National Academy of Sciences of the United States of America. 1989; 86(6): 2040–2044.</mixed-citation><mixed-citation xml:lang="en">Zocchi E. et al. Encapsulation of doxorubicin in liver-targeted erythrocytes increases the therapeutic index of the drug in a murine metastatic model. Proceedings of the National Academy of Sciences of the United States of America. 1989; 86(6): 2040–2044.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Rossi L. et al. Engineering erythrocytes for the modulation of drugs’ and contrasting agents’ pharmacokinetics and biodistribution. Advanced Drug Delivery Reviews. 2016; 106: 73–87.</mixed-citation><mixed-citation xml:lang="en">Rossi L. et al. Engineering erythrocytes for the modulation of drugs’ and contrasting agents’ pharmacokinetics and biodistribution. Advanced Drug Delivery Reviews. 2016; 106: 73–87.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Villa C. H. et al. Erythrocytes as Carriers for Drug Delivery in Blood Transfusion and Beyond. Transfusion Medicine Reviews. 2017; 31(1): 26–35.</mixed-citation><mixed-citation xml:lang="en">Villa C. H. et al. Erythrocytes as Carriers for Drug Delivery in Blood Transfusion and Beyond. Transfusion Medicine Reviews. 2017; 31(1): 26–35.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Kravtzoff R. et al. Erythrocytes as carriers for L-asparaginase. Methodological and mouse in-vivo studies. The Journal of pharmacy and pharmacology. 1990; 42(7): 473–476.</mixed-citation><mixed-citation xml:lang="en">Kravtzoff R. et al. Erythrocytes as carriers for L-asparaginase. Methodological and mouse in-vivo studies. The Journal of pharmacy and pharmacology. 1990; 42(7): 473–476.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Field W. N. et al. A comparison of the treatment of thyroidectomized rats with free thyroxine and thyroxine encapsulated in erythrocytes. International Journal of Pharmaceutics. 1989; 51(2): 175–178.</mixed-citation><mixed-citation xml:lang="en">Field W. N. et al. A comparison of the treatment of thyroidectomized rats with free thyroxine and thyroxine encapsulated in erythrocytes. International Journal of Pharmaceutics. 1989; 51(2): 175–178.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Harisa G.E. et al. Characterization of human erythrocytes as potential carrier for pravastatin: An in vitro study. International Journal of Medical Sciences. 2011; 8(3): 222–230.</mixed-citation><mixed-citation xml:lang="en">Harisa G.E. et al. Characterization of human erythrocytes as potential carrier for pravastatin: An in vitro study. International Journal of Medical Sciences. 2011; 8(3): 222–230.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Hu C. M. J. et al. Erythrocyte-inspired delivery systems. Advanced Healthcare Materials. 2012; 1(5): 537–547.</mixed-citation><mixed-citation xml:lang="en">Hu C. M. J. et al. Erythrocyte-inspired delivery systems. Advanced Healthcare Materials. 2012; 1(5): 537–547.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Favretto M.E. et al. Human erythrocytes as drug carriers: Loading efficiency and side effects of hypotonic dialysis, chlorpromazine treatment and fusion with liposomes. Journal of Controlled Release. 2013; 170(3): 343–351.</mixed-citation><mixed-citation xml:lang="en">Favretto M.E. [et al.] Human erythrocytes as drug carriers: Loading efficiency and side effects of hypotonic dialysis, chlorpromazine treatment and fusion with liposomes. Journal of Controlled Release. 2013; 170(3): 343–351.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Ihler G. M. Tsang H. C. Hypotonic hemolysis methods for entrapment of agents in resealed erythrocytes. Methods in enzymology. 1987; 149: 221–229.</mixed-citation><mixed-citation xml:lang="en">Ihler G. M. Tsang H. C. Hypotonic hemolysis methods for entrapment of agents in resealed erythrocytes. Methods in enzymology. 1987; 149: 221–229.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Magnani M. et al. Erythrocyte Engineering for Drug Delivery and Targeting. Texas. Eurekah.com. 2002; 151.</mixed-citation><mixed-citation xml:lang="en">Magnani M. et al. Erythrocyte Engineering for Drug Delivery and Targeting. Texas. Eurekah.com. 2002; 151.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Magnani M., DeLoach J. R. The Use of Resealed Erythrocytes as Carriers and Bioreactors: Advances in Experimental Medicine and Biology. Boston. Springer US. 1992; 341.</mixed-citation><mixed-citation xml:lang="en">Magnani M., DeLoach J. R. The Use of Resealed Erythrocytes as Carriers and Bioreactors: Advances in Experimental Medicine and Biology. Boston. Springer US. 1992; 341.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Skorokhod O. A. et al. Pharmacokinetics of erythrocyte-bound daunorubicin in patients with acute leukemia. Medical science monitor: international medical journal of experimental and clinical research. 2004; 10(4): 155–164.</mixed-citation><mixed-citation xml:lang="en">Skorokhod O. A. et al. Pharmacokinetics of erythrocyte-bound daunorubicin in patients with acute leukemia. Medical science monitor: international medical journal of experimental and clinical research. 2004; 10(4): 155–164.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Bhimavarapu R. et al. Resealed erythrocytes as a targeted drug delivery system – an overview. PHARMANEST An International Journal of Advances in Pharmaceutical Sciences. 2012; 3(1): 47–64.</mixed-citation><mixed-citation xml:lang="en">Bhimavarapu R. et al. Resealed erythrocytes as a targeted drug delivery system – an overview. PHARMANEST An International Journal of Advances in Pharmaceutical Sciences. 2012; 3(1): 47–64.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Wu Y. W. et al. Smart blood cell and microvesicle-based Trojan horse drug delivery: Merging expertise in blood transfusion and biomedical engineering in the field of nanomedicine. Transfusion and Apheresis Science. 2016; 54(2): 309–318.</mixed-citation><mixed-citation xml:lang="en">Wu Y. W. et al. Smart blood cell and microvesicle-based Trojan horse drug delivery: Merging expertise in blood transfusion and biomedical engineering in the field of nanomedicine. Transfusion and Apheresis Science. 2016; 54(2): 309–318.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Sprandel U. et al. Erythrocytes as Drug Carriers in Medicine. Boston, MA: Springer US. 1997; 149.</mixed-citation><mixed-citation xml:lang="en">Sprandel U. et al. Erythrocytes as Drug Carriers in Medicine. Boston, MA: Springer US. 1997; 149.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Sprandel U., Zöllner N. Osmotic fragility of drug carrier erythrocytes. Research in Experimental Medicine. 1985; 185(1): 77–85.</mixed-citation><mixed-citation xml:lang="en">Sprandel U., Zöllner N. Osmotic fragility of drug carrier erythrocytes. Research in Experimental Medicine. 1985; 185(1): 77–85.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Thorpe S. R. et al. Enzyme Therapy. V. In Vivo Fate of Erythrocyteentrapped β-Glucuronidase in β-Glucuronidase-deficient mice. Pediatric Research. 1975; 9(12): 918–923.</mixed-citation><mixed-citation xml:lang="en">Thorpe S. R. et al. Enzyme Therapy. V. In Vivo Fate of Erythrocyteentrapped β-Glucuronidase in β-Glucuronidase-deficient mice. Pediatric Research. 1975; 9(12): 918–923.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Tuhin F. T. et al. Essentials of Single-Cell Analysis: Series in BioEngineering. Berlin, Heidelberg: Springer Berlin Heidelberg. 2016; 325–346.</mixed-citation><mixed-citation xml:lang="en">Tuhin F. T. et al. Essentials of Single-Cell Analysis: Series in BioEngineering. Berlin, Heidelberg: Springer Berlin Heidelberg. 2016; 325–346.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Updike S. et al. Asparaginase entrapped in red blood cells: action and survival. Science. 1976; 193(4254): 681–683.</mixed-citation><mixed-citation xml:lang="en">Updike S. et al. Asparaginase entrapped in red blood cells: action and survival. Science. 1976; 193(4254): 681–683.</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Халахакун А.Д. Получение и стандартизация эритроцитарных носителей, инкапсулированных терпеноиндольными алкалоидными противоопухолевыми препаратами: автореф. дис. канд. фарм. н. Москва. 2018; 26.</mixed-citation><mixed-citation xml:lang="en">Halakhakun A.D. Production and standardization of erythrocyte carriers encapsulated with terpene-indole alkaloid antineoplastic drugs: Sc.D. Moscow. 2018; 26.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
