Polymer nanomedicines based on micelle-forming amphiphilic or water-soluble polymer-doxorubicin conjugates: comparative study of in vitro and in vivo properties related to the polymer carrier structure, composition, and hydrodynamic properties

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F20%3A00522842" target="_blank" >RIV/61388971:_____/20:00522842 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61389013:_____/20:00522842

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0168365920301413?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0168365920301413?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jconrel.2020.03.002" target="_blank" >10.1016/j.jconrel.2020.03.002</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Polymer nanomedicines based on micelle-forming amphiphilic or water-soluble polymer-doxorubicin conjugates: comparative study of in vitro and in vivo properties related to the polymer carrier structure, composition, and hydrodynamic properties

Popis výsledku v původním jazyce

The study compared the physico-chemical and biological properties of a water-soluble star-like polymer nanomedicine with three micellar nanomedicines formed by self-assembly of amphiphilic copolymers differing in their hydrophobic part (statistical, block and thermosensitive block copolymers). All nanomedicines showed a pH-responsive release of the drug, independent on polymer structure. Significant penetration of all polymer nanomedicines into tumor cells in vitro was demonstrated, where the most pronounced effect was observed for statistical- or diblock copolymer-based micellar systems. Tumor accumulation in vivo was dependent on the stability of the nanomedicines in solution, being the highest for the star-like system, followed by the most stable micellar nanomedicines. The star-like polymer nanomedicine showed a superior therapeutic effect. Since the micellar systems exhibited slightly lower systemic toxicity, they may exhibit the same efficacy as the star-like soluble system when administered at equitoxic doses. In conclusion, treatment efficacy of studied nanomedicines was directly controlled by the drug pharmacokinetics, namely by their ability to circulate in the bloodstream for the time needed for effective accumulation in the tumor due to the enhanced permeability and retention (EPR) effect. Easy and scalable synthesis together with the direct reconstitution possibility for nanomedicine application made these nanomedicines excellent candidates for further clinical evaluation.

Název v anglickém jazyce

Polymer nanomedicines based on micelle-forming amphiphilic or water-soluble polymer-doxorubicin conjugates: comparative study of in vitro and in vivo properties related to the polymer carrier structure, composition, and hydrodynamic properties

Popis výsledku anglicky

The study compared the physico-chemical and biological properties of a water-soluble star-like polymer nanomedicine with three micellar nanomedicines formed by self-assembly of amphiphilic copolymers differing in their hydrophobic part (statistical, block and thermosensitive block copolymers). All nanomedicines showed a pH-responsive release of the drug, independent on polymer structure. Significant penetration of all polymer nanomedicines into tumor cells in vitro was demonstrated, where the most pronounced effect was observed for statistical- or diblock copolymer-based micellar systems. Tumor accumulation in vivo was dependent on the stability of the nanomedicines in solution, being the highest for the star-like system, followed by the most stable micellar nanomedicines. The star-like polymer nanomedicine showed a superior therapeutic effect. Since the micellar systems exhibited slightly lower systemic toxicity, they may exhibit the same efficacy as the star-like soluble system when administered at equitoxic doses. In conclusion, treatment efficacy of studied nanomedicines was directly controlled by the drug pharmacokinetics, namely by their ability to circulate in the bloodstream for the time needed for effective accumulation in the tumor due to the enhanced permeability and retention (EPR) effect. Easy and scalable synthesis together with the direct reconstitution possibility for nanomedicine application made these nanomedicines excellent candidates for further clinical evaluation.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10606 - Microbiology

Projekt

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

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

Journal of Controlled Release

ISSN

0168-3659

e-ISSN

—

Svazek periodika

321

Číslo periodika v rámci svazku

10 May

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

16

Strana od-do

718-733

Kód UT WoS článku

000526179100049

EID výsledku v databázi Scopus

2-s2.0-85080982059