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Polymer nanomedicines based on micelle-forming amphiphilic or water-soluble polymer-doxorubicin conjugates: comparative study of in vitro and in vivo properties related to the polymer carrier structure, composition, and hydrodynamic properties

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    SYSNO ASEP0522842
    Document TypeJ - Journal Article
    R&D Document TypeJournal Article
    Subsidiary JČlánek ve WOS
    TitlePolymer nanomedicines based on micelle-forming amphiphilic or water-soluble polymer-doxorubicin conjugates: comparative study of in vitro and in vivo properties related to the polymer carrier structure, composition, and hydrodynamic properties
    Author(s) Braunová, Alena (UMCH-V) RID
    Chytil, Petr (UMCH-V) RID, ORCID
    Laga, Richard (UMCH-V) RID, ORCID
    Šírová, Milada (MBU-M) RID, ORCID
    Machová, Daniela (UMCH-V)
    Parnica, Jozef (UMCH-V)
    Říhová, Blanka (MBU-M) RID
    Janoušková, Olga (UMCH-V) RID, SAI, ORCID
    Etrych, Tomáš (UMCH-V) RID, ORCID
    Source TitleJournal of Controlled Release. - : Elsevier - ISSN 0168-3659
    Roč. 321, 10 May (2020), s. 718-733
    Number of pages16 s.
    Languageeng - English
    CountryNL - Netherlands
    Keywordspolymer micelles ; drug delivery ; EPR effect
    Subject RIVCD - Macromolecular Chemistry
    OECD categoryPolymer science
    Subject RIV - cooperationInstitute of Microbiology - Microbiology, Virology
    R&D ProjectsNV16-28600A GA MZd - Ministry of Health (MZ)
    GA17-13283S GA ČR - Czech Science Foundation (CSF)
    GA17-08084S GA ČR - Czech Science Foundation (CSF)
    LQ1604 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
    LTAUSA18083 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
    ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
    GA19-01417S GA ČR - Czech Science Foundation (CSF)
    Method of publishingLimited access
    Institutional supportUMCH-V - RVO:61389013 ; MBU-M - RVO:61388971
    UT WOS000526179100049
    EID SCOPUS85080982059
    DOI10.1016/j.jconrel.2020.03.002
    AnnotationThe study compared the physico-chemical and biological properties of a water-soluble star-like polymer nanomedicine with three micellar nanomedicines formed by self-assembly of amphiphilic copolymers differing in their hydrophobic part (statistical, block and thermosensitive block copolymers). All nanomedicines showed a pH-responsive release of the drug, independent on polymer structure. Significant penetration of all polymer nanomedicines into tumor cells in vitro was demonstrated, where the most pronounced effect was observed for statistical- or diblock copolymer-based micellar systems. Tumor accumulation in vivo was dependent on the stability of the nanomedicines in solution, being the highest for the star-like system, followed by the most stable micellar nanomedicines. The star-like polymer nanomedicine showed a superior therapeutic effect. Since the micellar systems exhibited slightly lower systemic toxicity, they may exhibit the same efficacy as the star-like soluble system when administered at equitoxic doses. In conclusion, treatment efficacy of studied nanomedicines was directly controlled by the drug pharmacokinetics, namely by their ability to circulate in the bloodstream for the time needed for effective accumulation in the tumor due to the enhanced permeability and retention (EPR) effect. Easy and scalable synthesis together with the direct reconstitution possibility for nanomedicine application made these nanomedicines excellent candidates for further clinical evaluation.
    WorkplaceInstitute of Macromolecular Chemistry
    ContactEva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358
    Year of Publishing2021
    Electronic addresshttps://www.sciencedirect.com/science/article/pii/S0168365920301413?via%3Dihub
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