Adaptable polymerization platform for therapeutics with tunable biodegradability

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F23%3A00576932" target="_blank" >RIV/61389013:_____/23:00576932 - isvavai.cz</a>

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S174270612300538X?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S174270612300538X?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.actbio.2023.09.004" target="_blank" >10.1016/j.actbio.2023.09.004</a>

Result language

angličtina

Original language name

Adaptable polymerization platform for therapeutics with tunable biodegradability

Original language description

Biodegradable polymer-based therapeutics have recently become essential drug delivery biomaterials for various bioactive compounds. Biodegradable and biocompatible polymer-based biomaterials fulfill the requirements of these therapeutics because they enable to obtain polymer biomaterials with optimized blood circulation, pharmacokinetics, biodegradability, and renal excretion. Herein, we describe an adaptable polymerization platform employed for the synthesis of long-circulating, stimulus-sensitive and biodegradable biomaterials, therapeutics, or theranostics. Four chain transfer agents (CTA) were designed and successfully synthesized for the reversible addition-fragmentation chain transfer polymerization, allowing the straightforward synthesis of hydrolytically biodegradable structures of block copolymers-based biomaterials. The controlled polymerization using the CTAs enables controlling the half-life of the hydrolytic degradation of polymer precursors in a wide range from 5 h to 21 days. Moreover, the antitumor drug pirarubicin (THP) was successfully conjugated to the polymer biomaterials via a pH-sensitive hydrazone bond for in vitro and in vivo experiments. Polymer conjugates demonstrated superior antitumor efficacy compared to basic linear polymer-based conjugates. Notably, the biodegradable systems, even though those with degradation in the order of hours were selected, increased the half-life of THP in the bloodstream almost two-fold. Indeed, the presented platform design enables the main chain-end specific attachment of targeting ligands or diagnostic molecules. The adaptable polymerization platform design allows tuning of the biodegradability rate, stimuli-sensitive drug bonding, and optimized pharmacokinetics to increase the therapy outcome and system targeting, thus allowing the preparation of targeted or theranostic polymer conjugates.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10404 - Polymer science

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2023

Confidentiality

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

Name of the periodical

Acta Biomaterialia

ISSN

1742-7061

e-ISSN

1878-7568

Volume of the periodical

171

Issue of the periodical within the volume

November

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

11

Pages from-to

417-427

UT code for WoS article

001092764300001

EID of the result in the Scopus database

2-s2.0-85171286088