Pharmacokinetics of intramuscularly administered thermoresponsive polymers

0564350 - ÚMCH 2023 RIV GB eng J - Journal Article
Groborz, Ondřej - Kolouchová, Kristýna - Pankrác, J. - Keša, P. - Kadlec, J. - Krunclová, Tereza - Pierzynová, A. - Šrámek, J. - Hovořáková, M. - Dalecká, L. - Pavlíková, Z. - Matouš, P. - Páral, P. - Loukotová, L. - Švec, P. - Beneš, Hynek - Štěpánek, L. - Dunlop, D. - Melo, C. V. - Šefc, L. - Slanina, T. - Beneš, J. - van Vlierberghe, S. - Hoogenboom, R. - Hrubý, Martin
Pharmacokinetics of intramuscularly administered thermoresponsive polymers.
Advanced Healthcare Materials. Roč. 11, č. 22 (2022), č. článku 2201344. ISSN 2192-2640. E-ISSN 2192-2659
R&D Projects: GA TA ČR(CZ) TO01000074; GA MŠMT(CZ) LTC19032; GA ČR(CZ) GA21-04166S
Research Infrastructure: Czech-BioImaging II - 90129
Institutional support: RVO:61389013
Keywords : biodistribution * LCST * poly(2,2-difluoroethyl)acrylamide
OECD category: Polymer science
Impact factor: 10, year: 2022
Method of publishing: Open access
https://onlinelibrary.wiley.com/doi/10.1002/adhm.202201344

Aqueous solutions of some polymers exhibit a lower critical solution temperature (LCST), that is, they form phase-separated aggregates when heated above a threshold temperature. Such polymers found many promising (bio)medical applications, including in situ thermogelling with controlled drug release, polymer-supported radiotherapy (brachytherapy), immunotherapy, and wound dressing, among others. Yet, despite the extensive research on medicinal applications of thermoresponsive polymers, their biodistribution and fate after administration remained unknown. Thus, herein, they studied the pharmacokinetics of four different thermoresponsive polyacrylamides after intramuscular administration in mice. In vivo, these thermoresponsive polymers formed depots that subsequently dissolved with a two-phase kinetics (depot maturation, slow redissolution) with half-lives 2 weeks to 5 months, as depot vitrification prolonged their half-lives. Additionally, the decrease of TCP of a polymer solution increased the density of the intramuscular depot. Moreover, they detected secondary polymer depots in the kidneys and liver, these secondary depots also followed two-phase kinetics (depot maturation and slow dissolution), with half-lives 8 to 38 days (kidneys) and 15 to 22 days (liver). Overall, these findings may be used to tailor the properties of thermoresponsive polymers to meet the demands of their medicinal applications. Their methods may become a benchmark for future studies of polymer biodistribution.

Permanent Link: https://hdl.handle.net/11104/0336178