Pharmacokinetics of Intramuscularly Administered Thermoresponsive Polymers

Abstract

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.

19F MRI In Vivo Monitoring of Gelatin-Based Hydrogels: 3D Scaffolds with Tunable Biodegradation toward Regenerative Medicine

“…This result is in line with our previous studies. 32,43 In that regard, our current data corroborate that DFEA is an excellent biocompatible tracer to track the in vivo distribution and biodegradation of hydrogels.…”

Cell-Interactive Gelatin-Based 19F MRI Tracers: An In Vitro Proof-of-Concept Study

“…Adipose tissue-derived stem cells (ASCs) were purchased from Lonza (Basel, Switzerland). Linear poly­[ N -(2,2-difluoroethyl)­acrylamide] ( M w = 42.0 kg/mol, Đ M = 1.11; CTA moiety was not removed) used as a standard in the 19 F relaxation study was prepared and characterized as described in our previously reported studies. , …”

“…Herein, we describe gel-MA- and gel-MA-AEMA-based hydrogels with covalently bound monomer N -(2,2-difluoroethyl)­acrylamide (DFEA), which enables us to monitor using 19 F MRI. ,− We study the kinetics of the hydrogels’ photopolymerization and the physicochemical properties (swelling degree, gel fraction (GF), storage modulus ( G ′), and loss modulus ( G ″)) as a function of their composition. Our composition/property analysis shows that all physicochemical properties can be tuned.…”

Thermoresponsive Triblock Copolymers as Widely Applicable 19F Magnetic Resonance Imaging Tracers

“…Nevertheless, triblock A- block -B- block -A or B- block -A- block -B copolymers have important advantages since they can take both states, including assembled particles and physically cross-linked gels as a function of their concentration. Together with feasible synthetic approaches, triblock copolymers can be seen as a smart toolbox, which covers almost the whole spectrum of potential medical applications of thermoresponsive/amphiphilic polymers. − Considering the non-biodegradability of polyacrylamides, these polymers in the form of particles or hydrogels can dissolve into individual polymer chains over a specific period of time, which can then be eliminated by renal excretion and therefore do not accumulate in the body. ,− …”