Pharmacokinetics of intramuscularly administered thermoresponsive polymers

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

doi:https://dx.doi.org/10.1002/adhm.202201344

Number of the records: 1

Pharmacokinetics of intramuscularly administered thermoresponsive polymers

1.

SYSNO ASEP	0564350
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Pharmacokinetics of intramuscularly administered thermoresponsive polymers
Author(s)	Groborz, Ondřej (UMCH-V)_{ORCID, RID} Kolouchová, Kristýna (UMCH-V)_{ORCID, RID} Pankrác, J. (CZ) Keša, P. (CZ) Kadlec, J. (IL) Krunclová, Tereza (UMCH-V)_ORCID Pierzynová, A. (CZ) Šrámek, J. (CZ) Hovořáková, M. (CZ) Dalecká, L. (CZ) Pavlíková, Z. (CZ) Matouš, P. (CZ) Páral, P. (CZ) Loukotová, L. (CZ) Švec, P. (CZ) Beneš, Hynek (UMCH-V)_{RID, ORCID} Štěpánek, L. (CZ) Dunlop, D. (CZ) Melo, C. V. (CZ) Šefc, L. (CZ) Slanina, T. (CZ) Beneš, J. (CZ) van Vlierberghe, S. (BE) Hoogenboom, R. (BE) Hrubý, Martin (UMCH-V)_{RID, ORCID}
Article number	2201344
Source Title	Advanced Healthcare Materials. - : Wiley - ISSN 2192-2640 Roč. 11, č. 22 (2022)
Number of pages	11 s.
Language	eng - English
Country	GB - United Kingdom
Keywords	biodistribution ; LCST ; poly(2,2-difluoroethyl)acrylamide
Subject RIV	CD - Macromolecular Chemistry
OECD category	Polymer science
R&D Projects	TO01000074 GA TA ČR - Technology Agency of the Czech Republic (TA ČR)
	LTC19032 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	GA21-04166S GA ČR - Czech Science Foundation (CSF)
Research Infrastructure	Czech-BioImaging II - 90129 - Ústav molekulární genetiky AV ČR, v. v. i.
Method of publishing	Open access
Institutional support	UMCH-V - RVO:61389013
UT WOS	000879463300001
EID SCOPUS	85141470993
DOI	10.1002/adhm.202201344
Annotation	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.
Workplace	Institute of Macromolecular Chemistry
Contact	Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358
Year of Publishing	2023
Electronic address	https://onlinelibrary.wiley.com/doi/10.1002/adhm.202201344

Number of the records: 1