Thermosensitive polymer nanoparticles for hyperthermia-triggered drug delivery – THERMONAPOL

Although upper critical solution temperature (UCST) polymers have an interesting potential for drug delivery applications, their use has been hampered so far by their lack of degradability. The goal of our project is to synthesize biodegradable diblock copolymers with UCST behavior based on PEGylated synthetic poly(amino acid)s bearing different pendant groups to encapsulate molecules of interest and to release them locally upon the application of mild hyperthermia (40-43°C). The UCST behavior will be studied as a function of polymer molar mass and concentration, pendant group nature/ratio, pH and ionic strength, experimentally as well as by coarse-grained molecular modelling. The optimal polymers will be formulated into nanoparticles and their ability to encapsulate corticosteroids and release them upon application of hyperthermia will be assessed. Nanoparticle toxicity/degradability will be evaluated on cell cultures and rat microsomes. Beyond the field of drug delivery nanomedicine, these novel biodegradable UCST polymers could find applications in other research fields such as cosmetics, bioseparation, or tissue engineering.