Thermoresponsive properties of star-shaped amphiphilic block copolymers with a cholic acid core and functional amine groups

Abstract Block copolymers having stimuli-responsive properties are gaining impetus in the design of drug and gene delivery systems for therapeutic purposes. Thermoresponsive polymers are particularly interesting due to the ease of control over their solution behavior in aqueous media. The fine tuning of the lower critical solution temperature (LCST) of such polymers is necessary to achieve a successful drug delivery. In this work, the thermoresponsive properties of block copolymers based on a bile acid are studied in aqueous media to determine the factors affecting the LCST. Poly(allyl glycidyl ether) (PAGE) and poly(ethylene glycol) (PEG) blocks were grafted from a cholic acid (CA) core to yield star-shaped block copolymers with 4 arms. The PAGE block was further functionalized to bear pendant amine groups. The addition of amine groups may be expected to improve the hydrophilicty of the polymers, but the functionalized polymers showed pronounced thermoresponsive properties and aggregation under physiological conditions. It is thus necessary to understand the changes of their solution properties for a better design of such polymers for drug delivery applications. In this work, we studied the effects of PEG length and of the amine groups on the LCST behavior in water at various salt concentrations. A shorter PEG chain of 21 repeat units shows a LCST of 16 °C, whereas a longer PEG of 41 repeat units failed to show thermoresponsiveness up to 80 °C and at concentrations up to 50 mg/mL. Functionalizing the allyl groups increased the LCST of the polymers. A salting-out effect was observed by a decrease in LCST and the presence of salt also promoted precipitation of the nanoparticles.