Hemocompatibility of layer-by-layer hyaluronic acid/heparin nanostructure coating on stainless steel for cardiovascular stents and its use for drug delivery.

In order to develop drug-eluting cardiovascular stents, stainless steel (SUS316L) sheets were coated with hyaluronic acid (HA) and heparin (HEP), and their in vitro characteristics and drug release pattern were investigated. The surface of stainless steel (SS) was treated with nitric acid and followed by anchoring aminotrimethoxysilane (ATMS), then a nanolayer of HA was covalently immobilized onto the surface. Heparin was then covalently bonded to the HA-immobilized SS substrate. After repeating 1 to 5 cycles, 1 to 5 layers polyelectrolyte complex (PEC) nanobrush of HA/HEP were resulted with the thickness ranging from 280 to 630 nm (measured with ellipsometry). A model drug (sirolimus) was loaded in the HA/HEP layers at a density ranging from 1.02 to 3.12 microg/cm2. The SS-ATMS-HA-HEP substrates were evidenced by X-ray photoelectron spectroscope (XPS), contact angle, and AFM measurement. The effect of this surface modification on the coagulation time of the resulting SS substrates was investigated. The results show that the multilayer HA/HEP stainless steel would exhibit higher anticoagulant activity than pure SS substrates. In addition, the results of the in vitro drug delivery study showed that release of sirolimus from the 5-layer-HA-HEP stainless steel was able to maintain more than 30 days. Thus layer-by-layer HA/HEP PEC can improve the hemocompatibility of SS surface and control the drug released rate by multiple layers of HA/HEP PEC. These results indicate that the multi-layer HA/HEP PEC coated stainless steel would be suitable for drug eluting stents.