Highly hydrophilic methacrylamide-based copolymers as precursors for polymeric nanomedicines containing anthracyclines

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F24%3A00580623" target="_blank" >RIV/61389013:_____/24:00580623 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/24:10479667 RIV/60461373:22310/24:43928992

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S001430572400017X?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S001430572400017X?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.eurpolymj.2024.112756" target="_blank" >10.1016/j.eurpolymj.2024.112756</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Highly hydrophilic methacrylamide-based copolymers as precursors for polymeric nanomedicines containing anthracyclines

Popis výsledku v původním jazyce

The crucial limitation of most low molecular weight cytostatic drugs, including anthracyclines, is their nonspecific biodistribution causing severe adverse effects during cancer treatment. Recently, nanomedicines such as polymer-based systems have been developed as advanced drug delivery systems. Herein, we report the design, synthesis, and characterization of highly water-soluble polymer-carriers based on N‑(1,3‑dihydroxyprop-2-yl)methacrylamide (DHPMA). Polymers differing in molecular weight, hydrodynamic size, and dispersity were synthesized via free or controlled radical polymerization and conjugated to an anthracycline drug pirarubicin (THP) via a pH-sensitive hydrazone bond achieving up to 21 wt% of THP. The DHPMA copolymers were extensively compared to the well-known drug delivery vectors, N-(2-hydroxypropyl)methacrylamide (HPMA)-based copolymers. Importantly, DHPMA-based conjugates showed excellent hydrophilicity exceeding that of HPMA-based copolymers and did not aggregate even after loading with THP reaching 21 wt%. The DHPMA-based polymer nanomedicines exhibited excellent cytotoxicity, body biodistribution, tumor accumulation, and antitumor efficacy, significantly reducing the side effects and toxicity comparable to HPMA-based systems, thus demonstrating their applicability and suitability as efficient drug carriers.

Název v anglickém jazyce

Highly hydrophilic methacrylamide-based copolymers as precursors for polymeric nanomedicines containing anthracyclines

Popis výsledku anglicky

The crucial limitation of most low molecular weight cytostatic drugs, including anthracyclines, is their nonspecific biodistribution causing severe adverse effects during cancer treatment. Recently, nanomedicines such as polymer-based systems have been developed as advanced drug delivery systems. Herein, we report the design, synthesis, and characterization of highly water-soluble polymer-carriers based on N‑(1,3‑dihydroxyprop-2-yl)methacrylamide (DHPMA). Polymers differing in molecular weight, hydrodynamic size, and dispersity were synthesized via free or controlled radical polymerization and conjugated to an anthracycline drug pirarubicin (THP) via a pH-sensitive hydrazone bond achieving up to 21 wt% of THP. The DHPMA copolymers were extensively compared to the well-known drug delivery vectors, N-(2-hydroxypropyl)methacrylamide (HPMA)-based copolymers. Importantly, DHPMA-based conjugates showed excellent hydrophilicity exceeding that of HPMA-based copolymers and did not aggregate even after loading with THP reaching 21 wt%. The DHPMA-based polymer nanomedicines exhibited excellent cytotoxicity, body biodistribution, tumor accumulation, and antitumor efficacy, significantly reducing the side effects and toxicity comparable to HPMA-based systems, thus demonstrating their applicability and suitability as efficient drug carriers.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10404 - Polymer science

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

European Polymer Journal

ISSN

0014-3057

e-ISSN

1873-1945

Svazek periodika

205

Číslo periodika v rámci svazku

7 February

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

12

Strana od-do

112756

Kód UT WoS článku

001159005300001

EID výsledku v databázi Scopus

2-s2.0-85182421277