Micelle-forming block copolymers tailored for inhibition of P-gp-mediated multidrug resistance: structure to activity relationship

0510951 - ÚMCH 2020 RIV CH eng J - Článek v odborném periodiku
Braunová, Alena - Kaňa, Martin - Kudláčová, Júlia - Kostka, Libor - Bouček, J. - Betka, J. - Šírová, Milada - Etrych, Tomáš
Micelle-forming block copolymers tailored for inhibition of P-gp-mediated multidrug resistance: structure to activity relationship.
Pharmaceutics. Roč. 11, č. 11 (2019), s. 1-22, č. článku 579. E-ISSN 1999-4923
Grant CEP: GA MZd(CZ) NV16-28600A
Institucionální podpora: RVO:61389013 ; RVO:61388971
Klíčová slova: polymer therapeutics * multidrug resistance * micelles
Obor OECD: Polymer science; Microbiology (MBU-M)
Impakt faktor: 4.421, rok: 2019
Způsob publikování: Open access
https://www.mdpi.com/1999-4923/11/11/579/pdf

Multidrug resistance (MDR) is often caused by the overexpression of efflux pumps, such as ABC transporters, in particular, P-glycoprotein (P-gp). Here, we investigate the di- and tri- block amphiphilic polymer systems based on polypropylene glycol (PPO) and copolymers of (N-(2-hydroxypropyl)methacrylamide) (PHPMA) as potential macromolecular inhibitors of P-gp, and concurrently, carriers of drugs, passively targeting solid tumors by the enhanced permeability and retention (EPR) effect. Interestingly, there were significant differences between the effects of di- and tri- block polymer-based micelles, with the former being significantly more thermodynamically stable and showing much higher P-gp inhibition ability. The presence of Boc-protected hydrazide groups or the Boc-deprotection method did not affect the physico-chemical or biological properties of the block copolymers. Moreover, diblock polymer micelles could be loaded with free PPO containing 5–40 wt % of free PPO, which showed increased P-gp inhibition in comparison to the unloaded micelles. Loaded polymer micelles containing more than 20 wt % free PPO showed a significant increase in toxicity. Thus, loaded diblock polymer micelles containing 5–15 wt % free PPO are potential candidates for in vitro and in vivo application as potent MDR inhibitors and drug carriers.
Trvalý link: http://hdl.handle.net/11104/0304086