Polyurethane-based thiomers: A new multifunctional copolymer platform for biomedical applications

摘要

During the past few decades, thiomers have attracted interest as responsive-polymers in the design of smart hydrogels, due to thiol reactivity to physical stimuli (i.e., pH, oxygen, UV/Vis irradiation). However, thiomer potentialities have been limited by their low thiolation degree and lack of multi-responsiveness to physical cues. In this work, a new class of thiomers with tailored thiolation degree and sensitivity to multiple physical stimuli was developed. To this aim, a polyurethane (33,000 Da) was synthesised from Poloxamer (R) 407, 1,6-diisocyanatohexanc and N-Boc diethanolamine. Secondary amino groups were exposed through Boc-removal (yield 80%, assessed by H-1 NMR) giving up to 4.5 x 10(20) +/- 1.8 x 10(19) -NH units/g(polymer) (Orange II Sodium Salt colorimetric assay) without polymer chemical degradation. Polymer thermo-responsiveness was proved by the increase in micelle hydrodynamic diameter upon system heating up to 45 degrees C and through estimated critical micellar temperatures. Thioglycolic acid grafting to exposed amines via carbodiimide chemistry was optimised to give up to 1.73 x 10(19) thiols/g(polymer) (Ellman's method), while minimising disulphide bond formation. Finally, the best storage conditions against oxidation were investigated by quantifying free thiols at different time points.