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

0522842 - ÚMCH 2021 RIV NL eng J - Journal Article
Braunová, Alena - Chytil, Petr - Laga, Richard - Šírová, Milada - Machová, Daniela - Parnica, Jozef - Říhová, Blanka - Janoušková, Olga - Etrych, Tomáš
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.
Journal of Controlled Release. Roč. 321, 10 May (2020), s. 718-733. ISSN 0168-3659. E-ISSN 1873-4995
R&D Projects: GA MZd(CZ) NV16-28600A; GA ČR(CZ) GA17-13283S; GA ČR(CZ) GA17-08084S; GA MŠMT(CZ) LQ1604; GA MŠMT(CZ) LTAUSA18083; GA MŠMT(CZ) ED1.1.00/02.0109; GA ČR(CZ) GA19-01417S
Institutional support: RVO:61389013 ; RVO:61388971
Keywords : polymer micelles * drug delivery * EPR effect
OECD category: Polymer science; Microbiology (MBU-M)
Impact factor: 9.776, year: 2020
Method of publishing: Limited access
https://www.sciencedirect.com/science/article/pii/S0168365920301413?via%3Dihub

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.
Permanent Link: http://hdl.handle.net/11104/0308163