Synthesis, characterization, and paclitaxel release from a biodegradable, elastomeric, poly(ester urethane)urea bearing phosphorylcholine groups for reduced thrombogenicity

Citation

Hong, Yi; Ye, Sang-Ho; Pelinescu, Anca L.; & Wagner, William R. (2012). Synthesis, characterization, and paclitaxel release from a biodegradable, elastomeric, poly(ester urethane)urea bearing phosphorylcholine groups for reduced thrombogenicity. Biomacromolecules, 13(11), 3686-3694.

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.

Keyword(s)

Animals
Biocompatible Materials
Blood Platelets
Cell Proliferation
Drug Carriers
Drug-Eluting Stents
Elasticity
Elastomers
Hydroxy Acids
Myocytes, Smooth Muscle
Paclitaxel
phosphorylcholine
Polyesters
Polymers
Propionates
Rats
Sheep
Tensile Strength
Vascular Grafting

Reference Type

Journal Article

Secondary Title

Biomacromolecules

Author(s)

Hong, Yi
Ye, Sang-Ho
Pelinescu, Anca L.
Wagner, William R.

Year Published

2012

Date Published

1352678400

Volume Number

13

Issue Number

11

Pages

3686-3694

ISSN/ISBN

1526-4602

DOI

10.1021/bm301158j