Premium
Pharmacokinetics of Intramuscularly Administered Thermoresponsive Polymers
Author(s) -
Groborz Ondřej,
Kolouchová Kristýna,
Pankrác Jan,
Keša Peter,
Kadlec Jan,
Krunclová Tereza,
Pierzynová Aneta,
Šrámek Jaromír,
Hovořáková Mária,
Dalecká Linda,
Pavlíková Zuzana,
Matouš Petr,
Páral Petr,
Loukotová Lenka,
Švec Pavel,
Beneš Hynek,
Štěpánek Lubomír,
Dunlop David,
Melo Carlos V.,
Šefc Luděk,
Slanina Tomáš,
Beneš Jiří,
Van Vlierberghe Sandra,
Hoogenboom Richard,
Hrubý Martin
Publication year - 2022
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.202201344
Subject(s) - biodistribution , lower critical solution temperature , polymer , depot , pharmacokinetics , kinetics , materials science , dissolution , chemistry , pharmacology , medicine , organic chemistry , biochemistry , copolymer , in vitro , archaeology , history , physics , quantum mechanics , composite material
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 T CP 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.