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<article 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" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="review-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Russian Journal of Biotherapy</journal-id><journal-title-group><journal-title xml:lang="en">Russian Journal of Biotherapy</journal-title><trans-title-group xml:lang="ru"><trans-title>Российский биотерапевтический журнал</trans-title></trans-title-group></journal-title-group><issn publication-format="print">1726-9784</issn><issn publication-format="electronic">1726-9792</issn><publisher><publisher-name xml:lang="en">Publishing House ABV Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">1540</article-id><article-id pub-id-type="doi">10.17650/1726-9784-2026-25-1-41-61</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>REVIEW</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>ОБЗОР ЛИТЕРАТУРЫ</subject></subj-group><subj-group subj-group-type="article-type"><subject>Review Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Local delivery of chemotherapy: innovative technologies and materials for local chemotherapy platforms</article-title><trans-title-group xml:lang="ru"><trans-title>Локальная доставка химиопрепаратов: инновационные технологии и материалы платформ для местной химиотерапии</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0001-7549-5947</contrib-id><name-alternatives><name xml:lang="en"><surname>Voznyuk</surname><given-names>Amina A.</given-names></name><name xml:lang="ru"><surname>Вознюк</surname><given-names>А. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>koudan1568@yandex.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8246-9846</contrib-id><name-alternatives><name xml:lang="en"><surname>Glinskaia</surname><given-names>Elizaveta G.</given-names></name><name xml:lang="ru"><surname>Глинская</surname><given-names>Е. Г.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>koudan1568@yandex.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0000-7935-7931</contrib-id><name-alternatives><name xml:lang="en"><surname>Demidov</surname><given-names>Egor S.</given-names></name><name xml:lang="ru"><surname>Демидов</surname><given-names>Е. С.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>koudan1568@yandex.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0007-7160-7802</contrib-id><name-alternatives><name xml:lang="en"><surname>Lugovoi</surname><given-names>Maksim E.</given-names></name><name xml:lang="ru"><surname>Луговой</surname><given-names>М. Е.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>www111www6376@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-9377-8118</contrib-id><name-alternatives><name xml:lang="en"><surname>Koudan</surname><given-names>Elizaveta V.</given-names></name><name xml:lang="ru"><surname>Кудан</surname><given-names>Е. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>koudan1568@yandex.ru</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">National University of Science and Technology “MISIS”</institution></aff><aff><institution xml:lang="ru">ФГАОУ ВО «Национальный исследовательский технологический университет “МИСИС”»</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2026-04-30" publication-format="electronic"><day>30</day><month>04</month><year>2026</year></pub-date><volume>25</volume><issue>1</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>41</fpage><lpage>61</lpage><history><date date-type="received" iso-8601-date="2025-06-19"><day>19</day><month>06</month><year>2025</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2026, ABV-Press</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2026, АБВ-пресс</copyright-statement><copyright-year>2026</copyright-year><copyright-holder xml:lang="en">ABV-Press</copyright-holder><copyright-holder xml:lang="ru">АБВ-пресс</copyright-holder><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://bioterapevt.abvpress.ru/jour/article/view/1540">https://bioterapevt.abvpress.ru/jour/article/view/1540</self-uri><abstract xml:lang="en"><p><bold>Background</bold>. Drug delivery systems are becoming an increasingly popular strategy to enhance the effectiveness of cancer treatment while reducing the systemic toxicity of chemotherapy. In recent years, the development of biomaterials and technologies for fabricating platforms (carriers) for controlled drug release has emerged as a key interdisciplinary research area at the intersection of materials science and oncology, leading to novel methods of carrier fabrication and drug incorporation.</p> <p><bold>Aim</bold>. To structure available data on the relationship between drug incorporation methods, platform fabrication techniques, and the resulting structural and functional properties of the carriers.</p> <p><bold>Materials and methods</bold>. Databases including Google Scholar, PubMed, Scopus, and ClinicalTrials.gov were used to identify and analyze studies from the past decade reporting on localized drug delivery platforms for cancer therapy. The selected studies were compared based on parameters such as porous and macrostructural morphology of the carriers, physicochemical characteristics, and controlled drug release profiles.</p> <p><bold>Results</bold>. It was found that drug release kinetics and duration depend on three main factors: the fabrication method of the carrier, its morphology (especially porosity), and the chemical composition of the polymer. Electrospinning of synthetic polymers is the most frequently applied method, enabling adjustable porosity and high specific surface area.</p> <p><bold>Conclusion</bold>. According to the reviewed studies, local drug delivery using carrier platforms contributes to an effective reduction in tumor cell proliferation and to the limitation of metastasis. This is associated with the achievement of higher and more sustained drug concentrations at the tumor site while simultaneously reducing circulating drug levels in the body, thereby decreasing systemic toxicity and increasing median overall survival. The advantages of local chemotherapy delivery, combined with technological advances, offer broad prospects for the development of safer and more effective chemotherapy strategies.</p></abstract><trans-abstract xml:lang="ru"><p><bold>Введение</bold>. Системы доставки химиопрепаратов становятся все более востребованной стратегией повышения эффективности лечения и снижения системной токсичности химиотерапии. В последние годы разработка биоматериалов и технологий изготовления платформ (носителей) для контролируемого высвобождения препаратов стала актуальной темой исследований на стыке материаловедения и онкологии, приведя к новым методам изготовления носителей и способов включения препаратов.</p> <p><bold>Цель исследования</bold> – структурировать данные о взаимосвязи между методом включения препарата, технологией изготовления платформы и ее структурно-функциональными свойствами.</p> <p><bold>Материалы и методы</bold>. Базы данных, включая Google Scholar, PubMed, Scopus и ClinicalTrials.gov, использованы для поиска и анализа исследований за последние десять лет, сообщающих об использовании локализованной доставки препаратов с помощью платформ для лечения онкологических заболеваний. Отобранные исследования сравнивались по ряду параметров, таких как формирование пористой и макроструктурной морфологии носителей, физико-химические характеристики и профиль контролируемого высвобождения химиопрепаратов.</p> <p><bold>Результаты</bold>. Обнаружено, что кинетика и продолжительность высвобождения препарата зависят от трех факторов: метода формирования носителя, его морфологии (особенно степени пористости) и химического состава полимера. Наиболее часто применяемой технологией является электроформование синтетических полимеров, обеспечивающее регулируемую пористость и высокую удельную поверхность.</p> <p><bold>Заключение</bold>. По данным рассмотренных исследований, локальная доставка препаратов с помощью носителей способствует эффективному снижению пролиферации опухолевых клеток и ограничению метастазирования. Это связано с достижением более высоких и длительно сохраняющихся концентраций препарата в зоне опухолевого роста при одновременном снижении его циркулирующих уровней в организме, что способствует уменьшению системной токсичности и увеличению медианы общей выживаемости пациентов. Преимущества локальной доставки химиопрепаратов в сочетании с технологическими достижениями открывают широкие перспективы для создания более безопасных и эффективных стратегий химиотерапии.</p></trans-abstract><kwd-group xml:lang="en"><kwd>drug delivery system</kwd><kwd>oncology</kwd><kwd>local recurrence</kwd><kwd>local chemotherapy</kwd><kwd>implantable device</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>система доставки препаратов</kwd><kwd>онкология</kwd><kwd>местный рецидив</kwd><kwd>локальная химиотерапия</kwd><kwd>имплантируемое устройство</kwd></kwd-group><funding-group><funding-statement xml:lang="en">This work was funded by the Ministry of Science and Higher Education of the Russian Federation under the strategic academic leadership program “Priority 2030” at National University of Science and Technology “MISIS”.</funding-statement><funding-statement xml:lang="ru">Работа выполнена при финансовой поддержке Министерства науки и высшего образования Российской Федерации в рамках программы стратегического академического лидерства «Приоритет-2030» в НИТУ МИСИС.</funding-statement></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Larrañeta E., Singh T.R.R., Donnelly R.F. Overview of the clinical current needs and potential applications for long-acting and implantable delivery systems. Long-Acting Drug Delivery Systems. Woodhead Publishing. 2022:1–16. DOI: 10.1016/B978-0-12-821749-8.00005-7</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Wolinsky J.B., Colson Y.L., Grinstaff M.W. Local drug delivery strategies for cancer treatment: gels, nanoparticles, polymeric films, rods, and wafers. J Control Release 2012;159(1):14–26. DOI: 10.1016/j.jconrel.2011.11.031</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Feng S.S., Chien S. Chemotherapeutic engineering: application and further development of chemical engineering principles for chemotherapy of cancer and other diseases. Chem Eng Sci 2003;58(18):4087–114. DOI: 10.1016/S0009-2509(03)00234-3</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Gottesman M.M., Fojo T., Bates S.E. Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer 2002;2(1):48–58. DOI: 10.1038/nrc706</mixed-citation></ref><ref id="B5"><label>5.</label><citation-alternatives><mixed-citation xml:lang="en">Hamid H.A., Ostrovsky O.V., Zykova E.V., Speransky D.L. Targeted drug delivery systems in breast cancer chemotherapy. Vestnik VolGMU = Journal of Volgograd State Medical University 2021;1:12–6. (In Russ.). DOI: 10.19163/1994-9480-2021-1(77)-12-16</mixed-citation><mixed-citation xml:lang="ru">Хамид Х.А., Островский О.В., Зыкова Е.В., Сперанский Д.Л. Адресные системы доставки лекарств в химиотерапии рака молочной железы. Вестник ВолГМУ. 2021;1:12–6. DOI: 10.19163/1994-9480-2021-1(77)-12-16 Hamid H.A., Ostrovsky O.V., Zykova E.V., Speransky D.L. Targeted drug delivery systems in breast cancer chemotherapy. Vestnik VolGMU = Journal of Volgograd State Medical University 2021;1:12–6. (In Russ.). DOI: 10.19163/1994-9480-2021-1(77)-12-16</mixed-citation></citation-alternatives></ref><ref id="B6"><label>6.</label><mixed-citation>Danhier F. To exploit the tumor microenvironment: Since the EPR effect fails in the clinic, what is the future of nanomedicine? J Control Release 2016;244(Pt A):108–21. DOI: 10.1016/j.jconrel.2016.11.015</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Langer R., Peppas N.A. Advances in biomaterials, drug delivery, and bionanotechnology. AICHE J 2003;49(12):2990–3006. DOI: 10.1002/aic.690491202</mixed-citation></ref><ref id="B8"><label>8.</label><citation-alternatives><mixed-citation xml:lang="en">Severin E.S. New approaches to targeted drug delivery to tumour cells. Uspekhi khimii = Russ Chem Rev 2015;84(1):43–60. (In Russ.). DOI: 10.1070/RCR4468</mixed-citation><mixed-citation xml:lang="ru">Северин Е.С. Новые подходы к избирательной доставке лекарственных препаратов в опухолевые клетки. Успехи химии 2015;84(1):43–60. DOI: 10.1070/RCR4468</mixed-citation></citation-alternatives></ref><ref id="B9"><label>9.</label><citation-alternatives><mixed-citation xml:lang="en">Postnov V.N., Naumysheva E.B., Korolev D.V., Galagudza M.M. Nanoscale carriers for drug delivery. Biotekhnosfera = Biotechnosphere 2013;6:16–27. (In Russ.).</mixed-citation><mixed-citation xml:lang="ru">Постнов В.Н., Наумышева Е.Б., Королев Д.В., Галагудза М.М. Наноразмерные носители для доставки лекарственных препаратов. Биотехносфера 2013;6:16–27.</mixed-citation></citation-alternatives></ref><ref id="B10"><label>10.</label><citation-alternatives><mixed-citation xml:lang="en">Pyataev N.A., Meltsaev G.G., Skopin P.I. et al. Targeted transport of antitumor chemopreparations: modern technologies and prospects of development. Povolzhskiy oncologicheskiy vestnik = Oncology Bulletin of the Volga Region 2012;3:47–58. (In Russ.).</mixed-citation><mixed-citation xml:lang="ru">Пятаев Н.А., Мельцаев Г.Г., Скопин П.И. и др. Таргетный транспорт противоопухолевых химиопрепаратов: современные технологии и перспективы развития. Поволжский онкологический вестник 2012;3:47–58.</mixed-citation></citation-alternatives></ref><ref id="B11"><label>11.</label><mixed-citation>Brem H. Polymers to treat brain tumours. Biomater 1990;11(9):699–701. DOI: 10.1016/0142-9612(90)90030-t</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Strobel O., Neoptolemos J., Jäger D., Büchler M.W. Optimizing the outcomes of pancreatic cancer surgery. Nat Rev Clin Oncol 2019;16(1):11–26. DOI: 10.1038/s41571-018-0112-1</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Talebian S., Foroughi J., Wade S.J. et al. Biopolymers for antitumor implantable drug delivery systems: recent advances and future outlook. Adv Mater 2018;30(31):e1706665. DOI: 10.1002/adma.201706665</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Obayemi J.D., Jusu S.M., Salifu A.A. et al. Degradable porous drug-loaded polymer scaffolds for localized cancer drug delivery and breast cell/tissue growth. Mater Sci Eng C Mater Biol Appl 2020;112:110794. DOI: 10.1016/j.msec.2020.110794</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Indolfi L., Ligorio M., Ting D.T. et al. A tunable delivery platform to provide local chemotherapy for pancreatic ductal adenocarcinoma. Biomaterials 2016;93:71–82. DOI: 10.1016/j.biomaterials.2016.03.044</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Youssef S.H., Kim S., Khetan R. et al. The development of 5-fluorouracil biodegradable implants: a comparative study of PCL/PLGA blends. J Drug Deliv Sci Tec 2023;81:104300. DOI: 10.1016/j.jddst.2023.104300</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Fleming A.B., Saltzman W.M. Pharmacokinetics of the carmustine implant. Clin Pharmacokinet 2002;41:403–19. DOI: 10.2165/00003088-200241060-00002</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Coburn J., Harris J., Zakharov A.D. et al. Implantable chemotherapy-loaded silk protein materials for neuroblastoma treatment. Int J Cancer 2017;140(3):726–35. DOI: 10.1002/ijc.30479</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Chen H., Wu J., Rahman M.S.U. et al. Dual drug-loaded PLGA fibrous scaffolds for effective treatment of breast cancer in situ. Biomater Adv 2023;148:213358. DOI: 10.1016/j.bioadv.2023.213358</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Hsu M.Y., Hsieh C.H., Huang Y.T. et al. Enhanced paclitaxel efficacy to suppress triple-negative breast cancer progression using metronomic chemotherapy with a controlled release system of Electrospun Poly-DL-Lactide-co-glycolide (PLGA) nanofibers. Cancers (Basel) 2021;13(13):3350. DOI: 10.3390/cancers13133350</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Ramachandran R., Junnuthula V R., Gowd G.S. et al. Theranostic 3-Dimensional nano brain-implant for prolonged and localized treatment of recurrent glioma. Sci Rep 2017;7(1):43271. DOI: 10.1038/srep43271</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Wang X., Wang L., Zong S. et al. Use of multifunctional composite nanofibers for photothermalchemotherapy to treat cervical cancer in mice. Biomater Sci 2019;7(9):3846–54. DOI: 10.1039/C9BM00756C</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Darbasizadeh B., Mortazavi S.A., Kobarfard F. et al. Electrospun Doxorubicin-loaded PEO/PCL core/sheath nanofibers for chemopreventive action against breast cancer cells. J Drug Delivery Sci Technol 2021;64(1):102576. DOI: 10.1016/j.jddst.2021.102576</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Han D., Serra R., Gorelick N. et al. Multi-layered core-sheath fiber membranes for controlled drug release in the local treatment of brain tumor. Sci Rep 2019;9(1):17936. DOI: 10.1038/s41598-019-54283-y</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Zhao J., Zhu Y., Ye C. et al. Photothermal transforming agent and chemotherapeutic co-loaded electrospun nanofibers for tumor treatment. Int J Nanomedicine 2019;14:3893–909. DOI:10.2147/IJN.S202876</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Martorana A., Puleo G., Miceli G.C. et al. Redox/NIR dual-responsive glutathione extended polyurethane urea electrospun membranes for synergistic chemo-photothermal therapy. Int J Pharm 2025;669:125108. DOI: 10.1016/j.ijpharm.2024.125108</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Wei W., Zarghami N., Abasi M. et al. Implantable magnetic nanofibers with ON–OFF switchable release of curcumin for possible local hyperthermic chemotherapy of melanoma. J Biomed Mater Res A 2022;110(4):851–60. DOI: 10.1002/jbm.a.37333</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Li J., Zhu J., Jia L. et al. Aqueous-based electrospun P (NIPAAm-co-AAc)/RSF medicated fibrous mats for dual temperature-and pH-responsive drug controlled release. RSC Adv 2020;10(1):323–31. DOI: 10.1039/C9RA08832F</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Park J.H., Seo H., Kim D.I. et al. Gold nanocage-incorporated poly(ε-caprolactone)(PCL) fibers for chemophotothermal synergistic cancer therapy. Pharmaceutics 2019;11(2):60. DOI: 10.3390/pharmaceutics11020060</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Li L., Yang G., Zhou G. et al. Thermally switched release from a nanogel-in-microfiber device. Adv Healthc Mater 2015;4(11):1658–63. DOI: 10.1002/adhm.201500267</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Yan E., Jiang J., Yang X. et al. pH-sensitive core-shell electrospun nanofibers based on polyvinyl alcohol/polycaprolactone as a potential drug delivery system for the chemotherapy against cervical cancer. J Drug Delivery Sci Technol 2019;55:101455. DOI: 10.1016/j.jddst.2019.101455</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Federico S., Martorana A., Pitarresi G. et al. Development of stimulus-sensitive electrospun membranes based on novel biodegradable segmented polyurethane as triggered delivery system for doxorubicin. Biomater Adv 2022;136:212769. DOI: 10.1016/j.bioadv.2022.212769</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Lahr C.A., Landgraf M., Sanchez-Herrero A. et al. A 3D-printed biomaterials-based platform to advance established therapy avenues against primary bone cancers. Acta Biomater 2020;118:69–82. DOI: 10.1016/j.actbio.2020.10.006</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Dang H.P., Shafiee A., Lahr C.A. et al. Local doxorubicin delivery via 3D‐printed porous scaffolds reduces systemic cytotoxicity and breast cancer recurrence in mice. Adv Therap 2020;3(9):2000056. DOI: 10.1002/adtp.202000056</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>Wang Y., Sun L., Mei Z. et al. 3D printed biodegradable implants as an individualized drug delivery system for local chemotherapy of osteosarcoma. Mater Des 2020;186:108336. DOI: 10.1016/j.matdes.2019.108336</mixed-citation></ref><ref id="B36"><label>36.</label><mixed-citation>Yi H.G., Choi Y.J., Kang K.S. et al. A 3D-printed local drug delivery patch for pancreatic cancer growth suppression. J Control Release 2016;238:231–41. DOI: 10.1016/j.jconrel.2016.06.015</mixed-citation></ref><ref id="B37"><label>37.</label><mixed-citation>Wei X., Liu C., Wang Z., Luo Y. 3D printed core-shell hydrogel fiber scaffolds with NIR-triggered drug release for localized therapy of breast cancer. Int J Pharm 2020;580:119219. DOI: 10.1016/j.ijpharm.2020.119219</mixed-citation></ref><ref id="B38"><label>38.</label><mixed-citation>Liu C., Wang Z., Wei X. et al. 3D printed hydrogel/PCL core/shell fiber scaffolds with NIR-triggered drug release for cancer therapy and wound healing. Acta Biomater 2021;131:314–25. DOI: 10.1016/j.actbio.2021.07.011</mixed-citation></ref><ref id="B39"><label>39.</label><mixed-citation>Bozuyuk U., Yasa O., Yasa I.C. et al. Light-triggered drug release from 3D-printed magnetic chitosan microswimmers. ACS nano 2018;12(9):9617–25. DOI: 10.1021/acsnano.8b05997</mixed-citation></ref><ref id="B40"><label>40.</label><mixed-citation>Kong X., Houzong R., Fu J. et al. Application of a novel thermo-sensitive injectable hydrogel in therapy in situ for drug accurate controlled release. J Biomed Mater Res B Appl Biomater 2020;108(8):3200–16. DOI: 10.1002/jbm.b.34658</mixed-citation></ref><ref id="B41"><label>41.</label><mixed-citation>Alexander A., Ajazuddin A., Khan J. et al. Formulation and evaluation of chitosan-based long-acting injectable hydrogel for PEGylated melphalan conjugate. J Pharm Pharmacol 2014;66(9):1240–50. DOI: 10.1111/jphp.12262</mixed-citation></ref><ref id="B42"><label>42.</label><mixed-citation>Al Sabbagh C., Seguin J., Agapova E. et al. Thermosensitive hydrogels for local delivery of 5-fluorouracil as neoadjuvant or adjuvant therapy in colorectal cancer. Eur. J. Pharm. Biopharm 2020;157:154–64. DOI: 10.1016/j.ejpb.2020.10.011</mixed-citation></ref><ref id="B43"><label>43.</label><mixed-citation>Yang X., Chen X., Wang Y. et al. Sustained release of lipophilic gemcitabine from an injectable polymeric hydrogel for synergistically enhancing tumor chemoradiotherapy. J Chem Eng 2020;396:125320. DOI: 10.1016/j.cej.2020.125320</mixed-citation></ref><ref id="B44"><label>44.</label><mixed-citation>Zentner G.M., Rathi R., Shih C. et al. Biodegradable block copolymers for delivery of proteins and water-insoluble drugs. J Control Release 2001;72(1–3):203–15. DOI: 10.1016/S0168-3659(01)00276-0</mixed-citation></ref><ref id="B45"><label>45.</label><mixed-citation>Zhou S., Zheng X., Yi K. et al. Temperature-ion-pH triple responsive gellan gum as in situ hydrogel for long-acting cancer treatment. Gels 2022;8(8):508. DOI: 10.3390/gels8080508</mixed-citation></ref><ref id="B46"><label>46.</label><mixed-citation>Xu X., Huang Z., Huang Z. et al. Injectable, NIR/pH-responsive nanocomposite hydrogel as long-acting implant for chemophotothermal synergistic cancer therapy. ACS Appl Mater Interfaces 2017;9(24):20361–75. DOI: 10.1021/acsami.7b02307</mixed-citation></ref><ref id="B47"><label>47.</label><mixed-citation>Jo Y.J., Gulfam M., Jo S.H. et al. Multi-stimuli responsive hydrogels derived from hyaluronic acid for cancer therapy application. Carbohydr Polym 2022;286:119303. DOI: 10.1016/j.carbpol.2022.119303</mixed-citation></ref><ref id="B48"><label>48.</label><mixed-citation>Sun H., Choi D., Heo J. et al. Studies on the drug loading and release profiles of degradable chitosan-based multilayer films for anticancer treatment. Cancers 2020;12(3):593. DOI: 10.3390/cancers12030593</mixed-citation></ref><ref id="B49"><label>49.</label><mixed-citation>Hsu B.B., Park M.H., Hagerman S.R., Hammond P.T. Multimonth controlled small molecule release from biodegradable thin films. Proc Natl Acad Sci USA 2014;111(33):12175–80. DOI: 10.1073/pnas.1323829111</mixed-citation></ref><ref id="B50"><label>50.</label><mixed-citation>Voznyuk A.A., Makarets Y.A., Advakhova D.Y. et al. Biodegradable local chemotherapy platform with prolonged and controlled release of doxorubicin for the prevention of local tumor recurrence. ACS Appl Bio Mater 2024;7(4):2472–87. DOI: 10.1021/acsabm.4c00078</mixed-citation></ref><ref id="B51"><label>51.</label><mixed-citation>Moreira A.F., Rodrigues C.F., Jacinto T.A. et al. Poly(vinyl alcohol)/chitosan layer-by-layer microneedles for cancer chemo-photothermal therapy. Int J Pharm 2020;576:118907. DOI: 10.1016/j.ijpharm.2019.118907</mixed-citation></ref><ref id="B52"><label>52.</label><mixed-citation>Jiang Y., Jin Y., Feng C. et al. Engineering hyaluronic acid microneedles loaded with Mn2+ and temozolomide for topical precision therapy of melanoma. Adv Healthc Mater 2024;13(8):2303215. DOI: 10.1002/adhm.202303215</mixed-citation></ref><ref id="B53"><label>53.</label><mixed-citation>Shaha S., Rodrigues D., Mitragotri S. Locoregional drug delivery for cancer therapy: preclinical progress and clinical translation. J Control Release 2024;367:737–67. DOI: 10.1016/j.jconrel.2024.01.072</mixed-citation></ref><ref id="B54"><label>54.</label><mixed-citation>Zhang H., Tian Y., Zhu Z. et al. Efficient antitumor effect of co-drug-loaded nanoparticles with gelatin hydrogel by local implantation. Sci Rep 2016;6(1):26546. DOI: 10.1038/srep26546</mixed-citation></ref><ref id="B55"><label>55.</label><mixed-citation>Wang M., Chen J., Li W. et al. Paclitaxel-nanoparticles-loaded double network hydrogel for local treatment of breast cancer after surgical resection. Mater Sci Eng C Mater Biol Appl 2020;114:111046. DOI: 10.1016/j.msec.2020.111046</mixed-citation></ref><ref id="B56"><label>56.</label><mixed-citation>Sabino I.J., Lima-Sousa R., Alves C.G. et al. Injectable in situ forming hydrogels incorporating dual-nanoparticles for chemo-photothermal therapy of breast cancer cells. Int J Pharm 2021;600:120510. DOI: 10.1016/j.ijpharm.2021.120510</mixed-citation></ref><ref id="B57"><label>57.</label><mixed-citation>Mohebian Z., Babazadeh M., Zarghami N., Mousazadeh H. Anticancer efficiency of curcumin-loaded mesoporous silica nanoparticles/nanofiber composites for potential postsurgical breast cancer treatment. J Drug Deliv Sci Technol 2021;61:102170. DOI: 10.1016/j.jddst.2020.102170</mixed-citation></ref><ref id="B58"><label>58.</label><mixed-citation>Wilhelm S., Tavares A.J., Dai Q. et al. Analysis of nanoparticle delivery to tumours. Nat Rev Mater 2016;1(5):16014. DOI: 10.1038/natrevmats.2016.14</mixed-citation></ref><ref id="B59"><label>59.</label><mixed-citation>Wang X., Burgess D.J. Drug release from in situ forming implants and advances in release testing. Adv Drug Deliv Rev 2021;178:113912. DOI: 10.1016/j.addr.2021.113912</mixed-citation></ref><ref id="B60"><label>60.</label><mixed-citation>Lugovoi M.E., Karshieva S.S., Usatova V.S. et al. The design of the spheroids-based in vitro tumor model determines its biomimetic properties. Biomater Adv 2025;169:214178. DOI: 10.1016/j.bioadv.2025.214178</mixed-citation></ref><ref id="B61"><label>61.</label><mixed-citation>Shapira-Furman T., Serra R., Gorelick N. et al. Biodegradable wafers releasing Temozolomide and Carmustine for the treatment of brain cancer. J Control Release 2019;295:93–101. DOI: 10.1016/j.jconrel.2018.12.048</mixed-citation></ref><ref id="B62"><label>62.</label><mixed-citation>Yanev P., van Tilborg G.A.F., Boere K.W.M. et al. Thermosensitive biodegradable hydrogels for local and controlled cerebral delivery of proteins: MRI-based monitoring of in vitro and in vivo protein release. ACS Biomater Sci Eng 2023;9(2):760–72. DOI: 10.1021/acsbiomaterials.2c01224</mixed-citation></ref><ref id="B63"><label>63.</label><mixed-citation>Ostergaard J., Nielsen L.H., Larsen S.W. et al. Development of a bio-relevant in vitro release testing method for subcutaneous and intramuscular oil depot formulations. J Drug Deliv Sci Technol 2024;102:106412. DOI: 10.1016/j.jddst.2024.106412</mixed-citation></ref><ref id="B64"><label>64.</label><mixed-citation>Sintzel M.B., Merkli A., Tabatabay C., Gurny R. Influence of irradiation sterilization on polymers used as drug carriers – a review. Drug Dev Ind Pharm 2008;23(9):857–78. DOI: 10.3109/03639049709148693</mixed-citation></ref><ref id="B65"><label>65.</label><mixed-citation>United States Pharmacopeia. Bacterial Endotoxins Test &lt; 85&gt;. USP-NF. 2017. DOI: 10.31003/uspnf_m98830_02_01</mixed-citation></ref><ref id="B66"><label>66.</label><mixed-citation>ICH Harmonised Tripartite Guideline Q1A(R2): Stability Testing of New Drug Substances and Products. International Conference on Harmonisation. 2003 URL: https://pharmadvisor.ru/document/tr3520/.</mixed-citation></ref><ref id="B67"><label>67.</label><mixed-citation>Guidance for Industry: Container Closure Systems for Packaging Human Drugs and Biologics. U.S. Food and Drug Administration. 1999. URL: https://www.fda.gov/media/70788/download.</mixed-citation></ref><ref id="B68"><label>68.</label><mixed-citation>GLIADEL® WAFER (carmustine implant), for intracranial use. U.S. Food and Drug Administration. 2018. URL: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020637s029lbl.pdf.</mixed-citation></ref><ref id="B69"><label>69.</label><mixed-citation>About ClinicalTrials.gov. National Library of Medicine. 2025 updated: June 0, 2024. URL: https://clinicaltrials.gov/about-site/about-ctg.</mixed-citation></ref><ref id="B70"><label>70.</label><mixed-citation>Bastiancich C., Malfanti A., Préat V., Rahman R. Rationally designed drug delivery systems for the local treatment of resected glioblastoma. Adv Drug Deliv Rev 2021;177:113951. DOI: 10.1016/j.addr.2021.113951</mixed-citation></ref></ref-list></back></article>
