Wang X T, Venkatraman S, Boey F, Loo S C, Tan L P
School of Materials Science & Engineering, Nanyang Technological University, N4.1-1-30, 50 Nanyang Avenue, Singapore 639798.
J Biomater Sci Polym Ed. 2007;18(11):1401-14. doi: 10.1163/156856207782246830.
Sirolimus-loaded bi-layer polymer matrices were fabricated and the effects of sirolimus release on proliferation and viability of human coronary artery smooth muscle cells (cSMCs) were investigated. Human cSMC recovery after sirolimus treatment and the attachment of human cSMC to sirolimus-eluting films were also studied. It was found that the released sirolimus inhibited growth factor stimulated human cSMC proliferation successfully. However, different drug doses appeared to have the same effect in the extent of inhibition of proliferation in this study. Cell viability was also observed to decrease with the presence of sirolimus and the attachment to sirolimus-eluting films was inhibited. The recovery of human cSMCs was found to be related to the duration of inhibition time by sirolimus. Longer inhibition resulted in a slower recovery, which suggests that sustained release is more effective than rapid release of a higher amount in the inhibition of cSMC proliferation. This observation may be important for the design of a drug-eluting stent.
制备了负载西罗莫司的双层聚合物基质,并研究了西罗莫司释放对人冠状动脉平滑肌细胞(cSMC)增殖和活力的影响。还研究了西罗莫司处理后人cSMC的恢复情况以及人cSMC与西罗莫司洗脱膜的附着情况。发现释放的西罗莫司成功抑制了生长因子刺激的人cSMC增殖。然而,在本研究中,不同药物剂量在抑制增殖程度上似乎具有相同的效果。还观察到随着西罗莫司的存在细胞活力下降,并且与西罗莫司洗脱膜的附着受到抑制。发现人cSMC的恢复与西罗莫司的抑制时间长短有关。抑制时间越长,恢复越慢,这表明在抑制cSMC增殖方面,持续释放比高剂量快速释放更有效。这一观察结果对于药物洗脱支架的设计可能很重要。