Key result
A novel drug-eluting stent formulation using a polyurethane matrix with 5% w/w probucol was developed to sustain drug release and promote endothelial cell proliferation in vitro.
A novel probucol-releasing polyurethane drug-eluting stent formulation was developed and optimized in vitro to potentially enhance endothelialization and reduce late stent thrombosis.
Requires in vivo validation before clinical testing; leaves open translation of this probucol-eluting formulation to reduced thrombosis.
The success of drug eluting stents (DESs) has been challenged by the manifestation of late stent thrombosis after DES implantation. The incomplete regeneration of the endothelial layer poststenting triggers adverse signaling processes precipitating in thrombosis. Various approaches have been attempted to prevent thrombosis, including the delivery of biological agents, such as estradiol, that promote endothelialization, and the use of natural polymers as coating materials. The underlying challenge has been the inability to release the biological agent in synchronization with the temporal sequence of vascular wound healing in vivo. The natural healing process of the endothelium after an injury starts after a week and may take up to a month in humans. This article presents a novel DES formulation using a hemocompatible polyurethane (PU) matrix to sustain the release of probucol (PB), an endothelial agonist, by exploiting the greater difference in the solubility parameters of PB and PU. This results in the formation of crystalline PB aggregates retarding drug release from PU. The physicochemical properties of PB in PU were confirmed using differential scanning calorimetry and X-ray diffraction. Drug-polymer compatibility was examined using infrared spectral analysis. Also, in vitro studies using primary human aortic endothelial cells resulted in the selection of 5% w/w PB as the optimal dose, to be further tested in vitro and in vivo. This work develops and tests a promising new DES formulation to enable faster endothelial cell proliferation poststenting, potentially minimizing the incidence and severity of thrombotic events after DES implantation.
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Vedantham et al. (2012) studied Stent thrombosis. Probucol-releasing polyurethane drug-eluting stent was evaluated on Drug release characteristics and endothelial cell proliferation. A novel drug-eluting stent formulation using a polyurethane matrix with 5% w/w probucol was developed to sustain drug release and promote endothelial cell proliferation in vitro.
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