Fine-tuning Thermoresponsive Functional Poly(ε-caprolactone)s to Enhance Micelle Stability and Drug Loading

Block copolymers synthesized by the ring-opening polymerization of γ-2-[2-(2-methoxyethoxy)ethoxy]ethoxy-ε-caprolactone (ME₃CL), γ-2-methoxyethoxy-ε-caprolactone (ME₁CL), and ε-caprolactone (CL) are reported. Previously, diblock copolymers of PME₃CL-b-PME₁CL displayed excellent thermoresponsive tunability (31-43 ⁰C) and self-assembled into micelles with moderate thermodynamic stability. In this report, two strategies are employed to enhance thermodynamic stability of PME₃CL/PME₁CL-type block copolymer micelles while maintaining their attractive thermoresponsive qualities: modification of the end group position and alteration of hydrophobic block composition by using both ME₁CL and CL. These new thermoresponsive amphiphilic block copolymers showed lower critical micelle concentration (CMC) values by one order of magnitude and formed thermodynamically stable micelles. Furthermore they demonstrated good biocompatibility and up to 4.97 wt% doxorubicin loading, more than double the amount loaded into the PME₃CL-type polymeric micelles previously reported.