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Hydrogel implants for transscleral drug delivery for retinoblastoma treatment

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    SYSNO ASEP0505096
    Document TypeJ - Journal Article
    R&D Document TypeJournal Article
    Subsidiary JČlánek ve WOS
    TitleHydrogel implants for transscleral drug delivery for retinoblastoma treatment
    Author(s) Cocarta, Ana-Irina (UMCH-V) RID, ORCID
    Hobzová, Radka (UMCH-V) RID, ORCID
    Širc, Jakub (UMCH-V) RID, ORCID
    Černá, T. (CZ)
    Hraběta, J. (CZ)
    Svojgr, K. (CZ)
    Pochop, P. (CZ)
    Kodetova, M. (CZ)
    Jedelská, J. (DE)
    Bakowsky, U. (DE)
    Uhlík, J. (CZ)
    Article number109799
    Source TitleMaterials Science & Engineering C-Materials for Biological Applications. - : Elsevier - ISSN 0928-4931
    Roč. 103, October (2019), s. 1-12
    Number of pages12 s.
    Languageeng - English
    CountryNL - Netherlands
    Keywordstransscleral delivery ; retinoblastoma ; topotecan
    Subject RIVCD - Macromolecular Chemistry
    OECD categoryPolymer science
    R&D ProjectsGA16-04863S GA ČR - Czech Science Foundation (CSF)
    LQ1604 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
    ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
    Method of publishingLimited access
    Institutional supportUMCH-V - RVO:61389013
    UT WOS000480664900066
    EID SCOPUS85066261744
    DOI10.1016/j.msec.2019.109799
    AnnotationRetinoblastoma (Rb) is the most common primary malignant intraocular tumor in children which develops from the retinal stem cells. Systemic chemotherapy is the typical therapeutic treatment and though most children survive Rb, they often lose their vision, or the eye needs to be enucleated. Regarding to the pure availability of the target tumor by systemic chemotherapy, the local anticancer drug administration would be advantageous to increase the local drug concentration and minimize adverse side effects of chemotherapy. The present paper describes a new hydrogel implant enabled to deliver therapeutically active doses of low molecular weight hydrophilic antitumor drugs topotecan and vincristine. The hydrogel implant is proposed as bi-layered with an inner hydrophilic layer from 2-hydroxyethyl methacrylate (HEMA) serving as a reservoir of the chemotherapeutic agent and an outer hydrophobic layer from 2-ethoxyethyl methacrylate (EOEMA) acting as a barrier to protect the surrounding vascularized tissue against cytotoxicity of the delivered chemotherapeutics. The experiments with enucleated pig eyes demonstrated the ability of tested drugs to diffuse through sclera and reach the vitreous humor. HEMA-based hydrogels were examined in terms of sorption, release and transport properties, showing the possibility of adjusting the loading capacity and diffusion of the drugs by the degree of crosslinking. The EOEMA-based gels proved to be an inert for drug sorption and diffusion. A chorioallantoic membrane assay demonstrated excellent biocompatibility of unloaded hydrogels, and in vitro experiments confirmed significant cytotoxicity of drug-loaded hydrogels against a Rb cell line (2 days for those topotecan-loaded and a minimum of 6 days for vincristine-loaded hydrogels). The bi-layered hydrogel implant can be considered promising for local administration of active agents to eye-globe for the treatment of Rb and also other ocular disorders.
    WorkplaceInstitute of Macromolecular Chemistry
    ContactEva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358
    Year of Publishing2020
    Electronic addresshttps://www.sciencedirect.com/science/article/pii/S0928493119307143?via%3Dihub
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