Development of epigallocatechin gallate-eluting polymeric stent and its physicochemical, biomechanical and biological evaluations.
Localized drug delivery from drug-eluting stents has been accepted as one of the most promising treatment methods for preventing restenosis after stenting. However, hypersensitivity reactions caused by their nonresorbable polymer coatings and bare-metal stents may result in serious clinical sequelae. Epigallocatechin-3-O-gallate (EGCG), the predominant catechin from tea, has been shown to exert anti-thrombotic, anti-inflammatory and anti-proliferative activities. In this study, it was hypothesized that sustainedly released EGCG from biodegradable poly(lactide-co-epsilon-caprolactone, PLCL) would suppress the proliferation of vascular smooth muscle cells (VSMCs). EGCG-releasing PLCL (E-PLCL) was prepared by blending PLCL with EGCG. The surface morphology, roughness and melting temperature of PLCL were not changed despite EGCG addition. EGCG was uniformly dispersed into E-PLCL and sustainedly released for periods up to 7 days by controlled diffusion rather than PLCL degradation. Moreover, EGCG did not affect tensile strength at break, but significantly increased the elastic modulus of PLCL. The proliferation of VSMCs onto E-PLCL was significantly suppressed although the cell attachment onto E-PLCL had been higher than that onto PLCL. On the other hand, EGCG-eluting polymeric stents were prepared with neither cracks nor webbings between struts, and their structural integrity was maintained without delamination or destruction. These results suggest that E-PLCL can be potentially applied for fabricating an EGCG-eluting vascular stent, namely an EGCG-eluting polymeric stent, or even an EGCG-releasing polymer-coated metal stent, to prevent thrombosis, inflammation and in-stent restenosis.
Han
Dong-Wook
DW
Department of Nanomedical Engineering, College of Nanoscience & Nanotechnology, Pusan National University, Busan 609-735, Korea. nanohan@pusan.ac.kr
Lee
Jun Jae
JJ
Jung
Duk-Young
DY
Park
Jong-Chul
JC
Hyon
Suong-Hyu
SH
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D002208:Caproates; D002392:Catechin / Q000031:analogs & derivatives / Q000378:metabolism; D016503:Drug Delivery Systems / Q000009:adverse effects; D054855:Drug-Eluting Stents; D007783:Lactones; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D011108:Polymers / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015607:Stents / Q000009:adverse effects*; D013718:Tensile Strength
D002208:Caproates; D007783:Lactones; D011108:Polymers; C121056:caprolactone; D002392:Catechin; C045651:epigallocatechin gallate