Polyurethane Organosilicate Nanocomposites as Blood Compatible Coatings

Abstract

Polymer clay nanocomposites (NCs) show remarkable potential in the field of drug delivery due to their enhanced barrier properties. It is hypothesised that well dispersed clay particles within the polymer matrix create a tortuous pathway for diffusing therapeutic molecules, thereby resulting in more sustained release of the drug. As coatings for medical devices, these materials can simultaneously modulate drug release and improve the mechanical performance of an existing polymer system without introducing additional materials with new chemistries that can lead to regulatory concerns. In this study, polyurethane organosilicate nanocomposites (PUNCs) coated onto stainless steel wires were evaluated for their feasibility as blood compatible coatings and as drug delivery systems. Heparin was selected as the model drug to examine the impact of silicate loading and modifier chain length in modulating release. Findings revealed that better dispersion was achieved from samples with lower clay loadings and longer alkyl chains. The blood compatibility of PUNCs as assessed by thrombin generation assays showed that the addition of silicate particles did not significantly decrease the thrombin generation lag time (TGT, p = 0.659) or the peak thrombin (p = 0.999) of polyurethane (PU). PUNC coatings fabricated in this research were not cytotoxic as examined by the cell growth inhibition assay and were uniformly intact, but had slightly higher growth inhibition compared to PU possibly due to the presence of organic modifiers (OM). The addition of heparin into PUNCs prolonged the TGT, indicating that heparin was still active after the coating process. Cumulative heparin release profiles showed that the majority of heparin released was from loosely attached residues on the surface of coils. The addition of heparin further prolonged the TGT as compared to coatings without added heparin, but a slight decrease in heparin activity was observed in the NCs. This was thought to be from competitive interactions between clay-heparin that influenced the formation of the ternary complex between heparin, ATIII thrombin. In summary, the feasibility of using PUNC as drug delivery coatings was shown by the good uniformity in the coating, absence of by-products from the coating process, and the release of active molecules without significantly interfering with their activity.