α,ω-Diphenylalanine-End-Capping of PEG-PPG-PEG Polymers Changes the Micelle Morphology and Enhances Stability of the Thermogel.

Pluronics F127 (P, PEG-PPG-PEG triblock copolymer) was coupled with diphenylalanine (FF) to prepare FF-end-capped Pluronics (FFPFF). With increasing temperature from 10 to 60 °C, the FFPFF self-assembled to vesicles in water. The unimer-to-vesicle transition accompanies endothermic enthalpy of 53.9 kcal/mol. Aqueous P and FFPFF solutions exhibited thermogelation in 15.0-24.0 wt %. The gel phase of FFPFF was stable up to 90 °C, whereas that of P turned into a sol again at 55-86 °C, indicating that end-capping with FF improved the gel stability against heat. In addition, the carboxylic acids of the FF end-groups can form coordination bonds with metal ions, and the gel modulus at 37 °C increased from 15-21 KPa (P) to 20-25 KPa (FFPFF) to 24-28 KPa (FFPFF-Zn), and the duration of gel against water-erosion increased from 24 h (P) to 60 h (FFPFF-Zn), leading to a useful biomaterial for sustained drug delivery. The FFPFF-Zn gels implanted in the rats' subcutaneous layer induced a mild inflammatory responses. Contrary to the previous end-capping of Pluronics by poly(lactic acid), polycarprolactone, carboxylic acid, and so on that weakened the gel stability, the diphenylalanine end-capping strengthened the stability of Pluronics gel against heat and water-erosion. This paper suggests that the control of polymer nanoassemblies directed by FF end-groups improves the mechanical properties and stability of the resulting thermogel and, thus, provides a useful drug delivery carrier with prolonged durability.