Behaviors of controlled drug release of magnetic-gelatin hydrogel coated stainless steel for drug-eluting-stents application

doi:10.1016/j.jmmm.2006.11.151

Journal of Magnetism and Magnetic Materials

Volume 310, Issue 2, Part 3, March 2007, Pages 2874-2876

https://doi.org/10.1016/j.jmmm.2006.11.151 Get rights and content

Abstract

The behavior of drug release controlled by magnetic fields (MF) for stainless steel coated with magnetic-gelatin (MAG-GE) hydrogel was investigated in this paper. X-ray photoelectron spectroscope (XPS) and vibrating sample magnetometer were used to evaluate the characterizations of MAG-GE hydrogel and the interaction with the surface of SUS316L. A model drug (sirolimus) was loaded to the MAG-GE hydrogel. When applying MF to the MAG-GE hydrogel, the sirolimus release rate of the magnetic hydrogel decreased by $\frac{1}{3}$ , comparing to that without the field. This suggests a “close” configuration of the MAG-GE hydrogel due to the aggregation of magnetic nanoparticles which reduced the pore size of MAG-GE hydrogel.

Introduction

Recently, drug-eluting stents with polymer coatings which act as drug reservoirs for controlled release over a period of several weeks or months have caused many researchers interests [1]. These drug-eluting stents can provide luminal scaffolding that virtually eliminates recoil and remodeling of the treated vessel, and the polymer coatings contain drugs that inhibit thrombosis, inflammation, or cellular proliferation [1]. Gelatin (GE) is extensively applied in drugs delivery systems due to their better swelling ratio and biocompatibility [2]. In addition, sirolimus is only effective when bound to sirolimus binding protein (FKBP) on smooth muscle cells [1]. It inhibits the proliferation of both rat and human smooth muscle cells in vitro [3] and reduces intima-thickening in models of vascular injury. Moreover, magnetic materials exhibit an intelligent property that can be triggered by magnetic field (MF) [4], [5]. The pore size of the magnetic hydrogels can be controlled by the external MF, thus the releasing rate of the drug can be varied. Therefore, in this work, sirolimus was encapsulated into magnetic-gelatin (MAG-GE) hydrogel coated on stainless steel (SS) to inhibit thrombosis formation and decrease restenosis. The drug releasing behavior of this novel magnetic-sensitive hydrogel for drug-eluting stents application was investigated in this paper.

Section snippets

Experiment

For the fabrication of sandwich-like structure of MAG-GE hydrogel (also called ferrogel) modified SS (SS-GE-ferrogels), the magnetic nanoparticles (ca. 5–10 nm) was prepared by in situ co-precipitation process [6]. The surface of SUS316L was anchored with aminotrimethoxy-silane (ATMS, 1 wt% toluene solution, Aldrich). Afterwards, gelatin (GE, Type A, Sigma) was covalently bonded via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC, 0.01M, Sigma) in order to form the amide bonding [7] between

Result and discussion

The XPS spectra (ESCALAB 250, Thermo VG Scientific, West Sussex, UK) of pure SS, SS-ATMS, SS-ATMS-GE substrates were shown in Fig. 1(b). The ${NH}_{2}$ peak (399.4 eV) of SS-ATMS was observed in the $N_{1 s}$ scan spectra, also indicated that ATMS have been immobilized onto SUS316L substrate. However, the ${NH}_{2}$ peak was shifted from 399.4 to 400.8 eV while the $GE - {COO}^{-}$ was conjugated with ATMS- ${NH}_{2}$ , implying the formation of amide bond (–CONH). Furthermore, the amino group of gelatin also was observed at the 401.1

Conclusion

Intelligent MAG-GE hydrogels have been successfully coated onto SUS316L substrates and the sirolimus-delivery can be modulated by switching “on” or “off” the MF. Moreover, the proliferation of the smooth muscle cells (TG/HA-VSMC human normal aorta smooth muscle cell from BCRC, Taiwan) was inhibited about 30% at 5-days in vitro incubation. The detail results would be reported in our future works. Based on these mechanisms, the sandwich-like structure of SS-GE-ferrogel may be potentially

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