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HPMA copolymer mebendazole conjugate allows systemic administration and possesses antitumour activity in vivo

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F22%3A00558143" target="_blank" >RIV/61388971:_____/22:00558143 - isvavai.cz</a>

  • Alternative codes found

    RIV/61389013:_____/22:00558143

  • Result on the web

    <a href="https://www.mdpi.com/1999-4923/14/6/1201" target="_blank" >https://www.mdpi.com/1999-4923/14/6/1201</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.3390/pharmaceutics14061201" target="_blank" >10.3390/pharmaceutics14061201</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    HPMA copolymer mebendazole conjugate allows systemic administration and possesses antitumour activity in vivo

  • Original language description

    Mebendazole and other benzimidazole antihelmintics, such as albendazole, fenbendazole, or flubendazole, have been shown to possess antitumour activity, primarily due to their microtubule-disrupting activity. However, the extremely poor water-solubility of mebendazole and other benzimidazoles, resulting in very low bioavailability, is a serious drawback of this class of drugs. Thus, the investigation of their antitumour potential has been limited so far to administering repeated high doses given peroral (p.o.) or to using formulations, such as liposomes. Herein, we report a fully biocompatible, water-soluble, HPMA copolymer-based conjugate bearing mebendazole (P-MBZ, Mw 28–33 kDa) covalently attached through a biodegradable bond, enabling systemic administration. Such an approach not only dramatically improves mebendazole solubility but also significantly prolongs the half-life and ensures tumour accumulation via an enhanced permeation and retention (EPR) effect in vivo. This P-MBZ has remarkable cytostatic and cytotoxic activities in EL-4 T-cell lymphoma, LL2 lung carcinoma, and CT-26 colon carcinoma mouse cell lines in vitro, with corresponding IC50 values of 1.07, 1.51, and 0.814 µM, respectively. P-MBZ also demonstrated considerable antitumour activity in EL-4 tumour-bearing mice when administered intraperitoneal (i.p.), either as a single dose or using 3 intermittent doses. The combination of P-MBZ with immunotherapy based on complexes of IL-2 and anti-IL-2 mAb S4B6, potently stimulating activated and memory CD8+ T cells, as well as NK cells, further improved the therapeutic effect.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30104 - Pharmacology and pharmacy

Result continuities

  • Project

    Result was created during the realization of more than one project. More information in the Projects tab.

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2022

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Pharmaceutics

  • ISSN

    1999-4923

  • e-ISSN

    1999-4923

  • Volume of the periodical

    14

  • Issue of the periodical within the volume

    6

  • Country of publishing house

    CH - SWITZERLAND

  • Number of pages

    11

  • Pages from-to

    1201

  • UT code for WoS article

    000816333500001

  • EID of the result in the Scopus database

    2-s2.0-85131853709