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
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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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