Isolation of methylene dianiline and aqueous-soluble biodegradation products from polycarbonate-polyurethanes

Polycarbonate-polyurethanes (PCNUs) have provided the medical device industry with practical alternatives to oxidation-sensitive polyether-urethanes (PEUs). To date, many studies have focused on PCNUs synthesized with 4,4′-methylene diphenyl-diisocyanate (MDI). The relative hydrolytic stability of this class of polyurethanes is actually quite surprising given the inherent hydrolytic potential of the aliphatic carbonate group. Yet, there has been little information reporting on the rationale for the materialʹs demonstrated hydrolytic stability. Recent work has shown that PCNU materials have a strong sensitivity towards hydrolysis when changes are made to their hard segment content and/or chemistry. However, knowledge is specifically lacking in regards of the identification of cleavage sites and the specific nature of the biodegradation products. Using high-performance liquid chromatography, radiolabel tracers and mass spectrometry, the current study provides insight into the distribution of biodegradation products from the enzyme-catalyzed hydrolysis of five different PCNUs. The hydrolytic sensitivity of the materials is shown to be related to the distribution of products, which itself is a direct consequence of unique micro-structures formed within the different materials. While an MDI-based polymer was shown to be the most hydrolytically stable material, it was the only PCNU that produced its diamine analog, in this case 4,4′-methylene dianiline (MDA), as a degradation product. Given the concern over aromatic diamine toxicity, this finding is important and highlights the fact that relative biostability is a distinct issue from that of degradation product toxicity, and that both must be considered separately when assessing the impact of biodegradation on biomaterial in vivo compatibility.