title: Synthesis, characterization, and paclitaxel release from a biodegradable, elastomeric, poly(ester urethane)urea bearing phosphorylcholine groups for reduced thrombogenicity.
abstract: Biodegradable polymers with high elasticity, low thrombogenicity, and drug loading capacity continue to be pursued for vascular engineering applications, including vascular grafts and stents. A biodegradable elastomeric polyurethane was designed as a candidate material for use as a drug-eluting stent coating, such that it was nonthrombogenic and could provide antiproliferative drug release to inhibit smooth muscle cell proliferation. A phosphorylcholine containing poly(ester urethane) urea (PEUU-PC) was synthesized by grafting aminated phosphorylcholine onto backbone carboxyl groups of a polyurethane (PEUU-COOH) synthesized from a soft segment blend of polycaprolactone and dimethylolpropionic acid, a hard segment of diisocyanatobutane and a putrescine chain extender. Poly(ester urethane) urea (PEUU) from a soft segment of polycaprolactone alone was employed as a control material. All of the synthesized polyurethanes showed high distensibility (>600%) and tensile strengths in the 20-35 MPa range. PEUU-PC experienced greater degradation than PEUU or PEUU-COOH in either a saline or lipase enzyme solution. PEUU-PC also exhibited markedly inhibited ovine blood platelet deposition compared with PEUU-COOH and PEUU. Paclitaxel loaded in all of the polymers during solvent casting continued to release for 5 d after a burst release in a 10% ethanol/PBS solution, which was utilized to increase the solubility of the releasate. Rat smooth muscle cell proliferation was significantly inhibited in 1 wk cell culture when releasate from the paclitaxel-loaded films was present. Based on these results, the synthesized PEUU-PC has promising functionality for use as a nonthrombogenic, drug eluting coating on metallic vascular stents and grafts.
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Hong
authors.forename: Sang-Ho
authors.initials: SH
authors.lastname: Ye
authors.forename: Anca L
authors.initials: AL
authors.lastname: Pelinescu
authors.forename: William R
authors.initials: WR
authors.lastname: Wagner
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D001792:Blood Platelets; D049109:Cell Proliferation; D004337:Drug Carriers; D054855:Drug-Eluting Stents; D004548:Elasticity; D020724:Elastomers / Q000737:chemistry; D006880:Hydroxy Acids / Q000737:chemistry; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010767:Phosphorylcholine / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D011108:Polymers; D011422:Propionates / Q000737:chemistry; D051381:Rats; D012756:Sheep / Q000097:blood; D013718:Tensile Strength; D058017:Vascular Grafting
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D020724:Elastomers; D006880:Hydroxy Acids; D011091:Polyesters; D011108:Polymers; D011422:Propionates; C497893:poly(ester urethane)urea; D010767:Phosphorylcholine; C016240:polycaprolactone; C110034:2,2-bis(hydroxymethyl)-propionic acid; D017239:Paclitaxel