Adaptable polymerization platform for therapeutics with tunable biodegradability

0576932 - ÚMCH 2024 RIV NL eng J - Journal Article
Hrochová, Michaela - Kotrchová, Lenka - Frejková, Markéta - Konefal, Rafal - Gao, S. - Fang, J. - Kostka, Libor - Etrych, Tomáš
Adaptable polymerization platform for therapeutics with tunable biodegradability.
Acta Biomaterialia. Roč. 171, November (2023), s. 417-427. ISSN 1742-7061. E-ISSN 1878-7568
R&D Projects: GA MZd(CZ) NU21-03-00273; GA MŠMT LX22NPO5102
Grant - others:AV ČR(CZ) MSM200502104; AV ČR(CZ) JSPS-22-01
Program: Program na podporu mezinárodní spolupráce začínajících výzkumných pracovníků; Bilaterální spolupráce
Institutional support: RVO:61389013
Keywords : HPMA * RAFT polymerization * drug delivery
OECD category: Polymer science
Impact factor: 9.7, year: 2022
Method of publishing: Open access
https://www.sciencedirect.com/science/article/pii/S174270612300538X?via%3Dihub

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.
Permanent Link: https://hdl.handle.net/11104/0346312