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 OPEN ACCESSCoatings 2012, 2 46 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.

Platelet interactions with polyurethane nanocomposites: effect of organic modifier terminal functionality

“…A disadvantage to this approach was the interactions that occurred between the bioactive molecule and the nanocomposite components. 13,14 In related research, it was also demonstrated that the organic molecules used to enhance dispersion of silicate nanoparticles can be released from PUNCs and impact biological interactions. 15,16 This study will address the hypothesis that OMs used to prepare the silicates incorporated into PU matrixes are surface expressed via diffusive migration and, through this expression, can directly impact on biological interactions.…”

“…Another approach is direct inclusion of bioactive molecules into polymers. Specifically, Chung et al 13 showed that heparin released from PUNCs perturbed blood-material interactions. A disadvantage to this approach was the interactions that occurred between the bioactive molecule and the nanocomposite components.…”

Thermal and Physico-Mechanical Characterizations of Thromboresistant Polyurethane Films

“…These properties, along with their excellent biocompatibility, have led to widespread research into their viability in biomedical applications. PU films have proven to be well suited for numerous medical-grade applications, including the use of protective coating on implantable devices [15]. Another example of PUs is the use as drug-release carriers, which either degrade to release drugs into a patient or have the drugs attached externally so that they will directly degrade over time [16].…”