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Microfluidic-assisted engineering of quasi-monodisperse pH-responsive polymersomes toward advanced platforms for the intracellular delivery of hydrophilic therapeutics

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    SYSNO ASEP0505875
    Document TypeJ - Journal Article
    R&D Document TypeJournal Article
    Subsidiary JČlánek ve WOS
    TitleMicrofluidic-assisted engineering of quasi-monodisperse pH-responsive polymersomes toward advanced platforms for the intracellular delivery of hydrophilic therapeutics
    Author(s) Calumby Albuquerque, Lindomar J. (UMCH-V)
    Sincari, Vladimir (UMCH-V) ORCID, RID
    Jäger, Alessandro (UMCH-V) RID, ORCID
    Konefal, Rafal (UMCH-V) RID, ORCID
    Pánek, Jiří (UMCH-V) RID, ORCID
    Černoch, Peter (UMCH-V) RID, ORCID
    Pavlova, Ewa (UMCH-V) RID
    Štěpánek, Petr (UMCH-V) RID, ORCID
    Giacomelli, F. C. (BR)
    Jäger, Eliezer (UMCH-V) ORCID, RID
    Source TitleLangmuir. - : AMER CHEMICAL SOC - ISSN 0743-7463
    Roč. 35, č. 25 (2019), s. 8363-8372
    Number of pages10 s.
    Languageeng - English
    CountryUS - United States
    Keywordsblock copolymers ; microfluidics ; self-assembled
    Subject RIVCD - Macromolecular Chemistry
    OECD categoryPolymer science
    R&D ProjectsGA17-09998S GA ČR - Czech Science Foundation (CSF)
    TN01000008 GA TA ČR - Technology Agency of the Czech Republic (TA ČR)
    8J18FR038 GA MŠk - Ministry of Education, Youth and Sports (MEYS)
    Method of publishingLimited access
    Institutional supportUMCH-V - RVO:61389013
    UT WOS000473248000020
    EID SCOPUS85067954153
    DOI10.1021/acs.langmuir.9b01009
    AnnotationThe extracellular and subcellular compartments are characterized by specific pH levels that can be modified by pathophysiological states. This scenario encourages the use of environmentally responsive nanomedicines for the treatment of damaged cells. We have engineered doxorubicin (DOX)-loaded pH-responsive polymersomes using poly([N-(2-hydroxypropyl)]methacrylamide)-b-poly[2-(diisopropylamino)ethyl methacrylate] block copolymers (PHPMAm-b-PDPAn). We demonstrate that, by taking advantage of the microfluidic technology, quasi-monodisperse assemblies can be created. This feature is of due relevance because highly uniform nanoparticles commonly exhibit more consistent biodistribution and cellular uptake. We also report that the size of the polymer vesicles can be tuned by playing with the inherent mechanical parameters of the microfluidic protocol. This new knowledge can be used to engineer size-specific nanomedicines for enhanced tumor accumulation if the manufacturing is performed with previous knowledge of tumor characteristics (particularly the degree of vascularity and porosity). The pH-dependent DOX release was further investigated evidencing the ability of polymersome to sustain encapsulated hydrophilic molecules when circulating in physiological environment (pH 7.4). This suggests nonrelevant drug leakage during systemic circulation. On the other hand, polymersome disassembly in slightly acid environments takes place enabling fast DOX release, thereby making the colloidal carriers highly cytotoxic. These features encourage the use of such advanced pH-responsive platforms to target damaged cells while preserving healthy environments during systemic circulation.
    WorkplaceInstitute of Macromolecular Chemistry
    ContactEva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358
    Year of Publishing2020
    Electronic addresshttps://pubs.acs.org/doi/10.1021/acs.langmuir.9b01009
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