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Development and properties of a new doxorubicin carrier based on surface-modified iron zero-valent microparticles with high encapsulation efficiency and the possibility of its controlled release

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dc.title Development and properties of a new doxorubicin carrier based on surface-modified iron zero-valent microparticles with high encapsulation efficiency and the possibility of its controlled release en
dc.title Разработка и свойства нового носителя доксорубицина на основе поверхностно-модифицированных микрочастиц ноль-валентного железа с высокой эффективностью инкапсуляции и возможностью его контролируемого высвобождения ru
dc.contributor.author Di Martino, Antonio
dc.contributor.author Vlasov, Sergei S.
dc.contributor.author Guryev, Artem M.
dc.contributor.author Yusubov, Mekham S.
dc.contributor.author Postnikov, Pavel S.
dc.contributor.author Belousov, Mikhail V.
dc.relation.ispartof Bulletin of Siberian Medicine
dc.identifier.issn 1682-0363 Scopus Sources, Sherpa/RoMEO, JCR
dc.date.issued 2019
utb.relation.volume 18
utb.relation.issue 2
dc.citation.spage 69
dc.citation.epage 79
dc.type article
dc.language.iso en
dc.publisher Siberian State Medical University
dc.identifier.doi 10.20538/1682-0363-2019-2-69-79
dc.relation.uri https://bulletin.tomsk.ru/jour/article/view/2306
dc.subject doxorubicin en
dc.subject chitosan en
dc.subject zerovalent iron microparticles en
dc.subject drug delivery en
dc.subject stimuli responsive carrier en
dc.subject controlled release en
dc.description.abstract Currently, chemotherapy combined with surgery and radiation therapy is the most effective treatment for cancer. At the same time, the use of this method is accompanied by serious side effects caused by the lack of specificity of most chemotherapeutic agents. In this regard, the development of drug delivery systems (DDS) capable of addressing a chemotherapeutic agent to cancer cells, as well as its controlled release, is a promising approach for the effective treatment of cancer. The aim of the study is to synthesize a new DDS based on surface-modified microparticles of zero-valent iron, to study its properties as a carrier of a chemotherapeutic agent (encapsulation efficiency, loading capacity, possibility of controlled release of a chemotherapeutic agent) and safety. Materials and methods. The microparticles were synthesised by reduction of iron (III) chloride with sodium borohydride followed by in situ surface modification by 4-carboxybenzyldiazonium tosylate. To confirm the occurrence of the reaction, FTIR spectroscopy (Nicolet iS5 Infrared Spectrometer (Thermo Scientific, USA)) was used. Hydrodynamic diameter and surface charge of the microparticles in solution were investigated by dynamic light scattering (DLS) and z-potential. DOX release studies were performed in simulated physiological conditions (pH 3.3; 5.5; 7.4) to evaluate the effect of the external pH on the release rate. Release studies under ultrasound irradiation were performed simultaneously in the same conditions. The effect of surface modification on encapsulation efficiency was evaluated at various pH values (3.3; 5.5; 7.4) and doxorubicin concentrations (0.2; 0.35; 0.5; 0.75; 1.0 mg/ml). To demonstrate the safety of the developed system, cytotoxicity studies were performed on HeLa cell lines (ATCC® CCL-2™). Results. An original method of preparation of the drug carrier, based on iron zero-valent microparticles with covalently attached chitosan (Fe-CS) on their surface was proposed. Prepared microparticles demonstrated high encapsulation efficiency, drug loading capacity of DOX (0.9 mg per 1 mg of Fe-CS microparticles), low cytotoxicity and also a possibility to modulate the release rate by ultrasound irradiation and by changing pH of the external environment. Conclusion. A carrier based on microparticles of zero-valent iron with covalently attached to the surface chitosan (Fe-CS) was obtained. The efficiency of encapsulation, the loading capacity of doxorubicin was determined and the possibility of its controlled release under the influence of an ultrasonic field at different pH values was confirmed. In an in vitro experiment on the HeLa cell line (ATCC® CCL-2™), no toxicity was established for all samples (Fe0, Fe-COOH и Fe-CS), regardless of their concentration. © 2019 Siberian State Medical University. All rights reserved. en
utb.faculty University Institute
dc.identifier.uri http://hdl.handle.net/10563/1009049
utb.identifier.obdid 43880575
utb.identifier.scopus 2-s2.0-85070564983
utb.identifier.wok 000480425600008
utb.source j-scopus
dc.date.accessioned 2019-09-19T07:56:13Z
dc.date.available 2019-09-19T07:56:13Z
dc.description.sponsorship TPU development project
dc.rights Attribution 4.0 International
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.rights.access openAccess
utb.contributor.internalauthor Di Martino, Antonio
utb.fulltext.sponsorship The study was supported by the TPU development project.
utb.wos.affiliation [Di Martino, A.; Vlasov, S. S.; Yusubov, M. S.; Postnikov, P. S.; Belousov, M., V] NR TPU, 30 Lenin Av, Tomsk 634050, Russia; [Vlasov, S. S.; Guryev, A. M.; Yusubov, M. S.; Belousov, M., V] SSMU, 2 Moscow Tract, Tomsk 634050, Russia; [Di Martino, A.] Tomas Bata Univ Zlin, 5678 Tr Tomas Bata, Zlin 76001, Czech Republic; [Postnikov, P. S.] Univ Chem & Technol, Prague 16628, Czech Republic
utb.scopus.affiliation National Research Tomsk Polytechnic University (NR TPU), 30 Lenin Av., Tomsk, 634050, Russian Federation; Siberian State Medical University (SSMU), 2, Moscow Tract, Tomsk, 634050, Russian Federation; Tomas Bata University in Zlin, 5678, Tr. Tomas Bata, Zlin, 760 01, Czech Republic; University of Chemistry and Technology, Prague, 166 28, Czech Republic
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