Počet záznamů: 1
HPMA copolymer mebendazole conjugate allows systemic administration and possesses antitumour activity in vivo
- 1.
SYSNO ASEP 0558143 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název HPMA copolymer mebendazole conjugate allows systemic administration and possesses antitumour activity in vivo Tvůrce(i) Studenovský, Martin (UMCH-V) RID, ORCID
Rumlerová, Anna (UMCH-V)
Kovářová, Jiřina (MBU-M)
Dvořáková, Barbora (MBU-M) RID
Sivák, Ladislav (MBU-M) RID
Kostka, Libor (UMCH-V) RID, ORCID
Berdár, Daniel (MBU-M)
Etrych, Tomáš (UMCH-V) RID, ORCID
Kovář, Marek (MBU-M) RID, ORCIDČíslo článku 1201 Zdroj.dok. Pharmaceutics. - : MDPI
Roč. 14, č. 6 (2022)Poč.str. 11 s. Jazyk dok. eng - angličtina Země vyd. CH - Švýcarsko Klíč. slova mebendazole ; drug delivery ; cancer therapy Vědní obor RIV CD - Makromolekulární chemie Obor OECD Polymer science Vědní obor RIV – spolupráce Mikrobiologický ústav - Farmakologie a lékárnická chemie CEP GA19-05649S GA ČR - Grantová agentura ČR LTAUSA18083 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora UMCH-V - RVO:61389013 ; MBU-M - RVO:61388971 UT WOS 000816333500001 EID SCOPUS 85131853709 DOI 10.3390/pharmaceutics14061201 Anotace 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. Pracoviště Ústav makromolekulární chemie Kontakt Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358 Rok sběru 2023 Elektronická adresa https://www.mdpi.com/1999-4923/14/6/1201
Počet záznamů: 1