title: Development of a probucol-releasing antithrombogenic drug eluting stent.
abstract: 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.
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: Kumar
authors.initials: K
authors.lastname: Vedantham
authors.forename: Somali
authors.initials: S
authors.lastname: Chaterji
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Kim
authors.forename: Kinam
authors.initials: K
authors.lastname: Park
mesh_terms: D001011:Aorta / Q000166:cytology / Q000187:drug effects; D002152:Calorimetry, Differential Scanning / Q000379:methods; D049109:Cell Proliferation; D002627:Chemistry, Physical / Q000379:methods; D016503:Drug Delivery Systems; D054855:Drug-Eluting Stents; D042783:Endothelial Cells / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D008422:Materials Testing; D008956:Models, Chemical; D010973:Platelet Adhesiveness; D011108:Polymers / Q000737:chemistry; D011140:Polyurethanes; D011341:Probucol / Q000008:administration & dosage*; D012995:Solubility; D013927:Thrombosis / Q000188:drug therapy; D014945:Wound Healing
chemical_list: D005343:Fibrinolytic Agents; D011108:Polymers; D011140:Polyurethanes; D011341:Probucol