Synthesis of biomedical, fluorescence-labelled polyesterurethanes for the investigation of their degradation

The synthesis and characterization of fluorescence-labelled, phase segregating block polyesterurethanes based on the known biocompatible and degradable materials poly[(R)-3-hydroxybutyric acid] (PHB), poly(epsilon-caprolactone) (PCL), and poly[(epsilon-caprolactone)-co-glycolide] (PCL/PGA) is described. To introduce fluorescence labels in the amorphous domains of the polymers, phenacyl 10,11-dihydroxyundecanoate (PDUA) was synthesized and copolymerized with a PHB diol, a PCL diol, and aliphatic diisocyanates. After cleavage of the protecting group (without degradation of the polymer backbone), the carboxyl group was reacted with a fluorescent amine (dansylcadaverine) in the presence of 4,6-diphenylthieno[3,4-d]-1,3-dioxol-2-one 5,5-dioxide (Steglich reagent). Also a polymer containing C-13-labelled carboxy groups was synthesized and the labelling reaction monitored by C-13 NMR spectroscopy. To introduce fluorescence labels in the hard segment of the polymers, a new low-molecular-weight diol based on poly[(R)-hydroxybutyric acid] and containing protected carboxy groups was synthesized. After the deprotection, the carboxy groups were reacted with a fluorescent amine (dansylcadaverine) in the presence of an activating system based on dicyclohexylcarbodiimide. The labelled PHB diol was then copolymerized with a poly[(epsilon-caprolactone)-co-glycolide] diol and an aliphatic diisocyanate. The so obtained fluorescence-labelled block polyesterurethanes are promising materials for the investigation of the biocompatibility and degradation of the corresponding, non-labelled materials (DegraPol(R)) by means of fluorescence-aided microscopic and spectroscopic techniques.