Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, China.
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Henan, Zhengzhou 450052, China.
Eur J Pharm Sci. 2024 Jan 1;192:106610. doi: 10.1016/j.ejps.2023.106610. Epub 2023 Oct 16.
Arterial restenosis caused by intimal hyperplasia (IH) is a serious complication after vascular interventions. In the rat carotid balloon injury model, we injected phosphate buffer saline (PBS), rapamycin-phosphate buffer saline suspension (RPM-PBS), blank fibrin glue (FG) and rapamycin-fibrin glue (RPM-FG) around the injured carotid artery under ultrasound guidance and observed the inhibitory effect on IH.
The properties of RPM-FG in vitro were verified by scanning electron microscopy (SEM) and determination of the drug release rate. FG metabolism in vivo was observed by fluorescence imaging. The rat carotid balloon injury models were randomly classified into 4 groups: PBS group (control group), RPM-PBS group, FG group, and RPM-FG group. Periadventitial administration was performed by ultrasound-guided percutaneous puncture on the first day after angioplasty. Carotid artery specimens were analyzed by immunostaining, Evans blue staining and hematoxylin-eosin staining.
The RPM particles showed clustered distributions in the FG block. The glue was maintained for a longer time in vivo (> 14 days) than in vitro (approximately 7 days). Two-component liquid FG administered by ultrasound-guided injection completely encapsulated the injured artery before coagulation. The RPM-FG inhibited IH after carotid angioplasty vs. control and other groups. The proliferation of vascular smooth muscle cells (VSMCs) was significantly inhibited during neointima formation, whereas endothelial cell (EC) repair was not affected.
Periadventitial delivery of RPM-FG contributed to inhibiting IH in the rat carotid artery injury model without compromising re-endothelialization. Additionally, FG provided a promising platform for the future development of a safe, effective, and minimally invasive perivascular drug delivery method to treat vascular disease.
内膜增生（IH）引起的动脉再狭窄是血管介入后的严重并发症。在大鼠颈动脉球囊损伤模型中，我们在超声引导下于损伤颈动脉周围注射磷酸盐缓冲盐水（PBS）、雷帕霉素-磷酸盐缓冲盐水混悬液（RPM-PBS）、空白纤维蛋白胶（FG）和雷帕霉素-纤维蛋白胶（RPM-FG），观察其对 IH 的抑制作用。
通过扫描电子显微镜（SEM）和药物释放率测定验证 RPM-FG 的体外性质。通过荧光成像观察 FG 在体内的代谢。将大鼠颈动脉球囊损伤模型随机分为 4 组：PBS 组（对照组）、RPM-PBS 组、FG 组和 RPM-FG 组。在血管成形术后第一天通过超声引导经皮穿刺行周向鞘内给药。通过免疫染色、伊文思蓝染色和苏木精-伊红染色分析颈动脉标本。
RPM 颗粒在 FG 块中呈聚集分布。胶体内保留时间较体外（约 7 天）延长（>14 天）。通过超声引导注射的双组分液体 FG 在凝固前完全包裹损伤的动脉。与对照组和其他组相比，颈动脉血管成形术后 RPM-FG 抑制 IH。在新生内膜形成过程中，血管平滑肌细胞（VSMCs）的增殖受到明显抑制，而内皮细胞（EC）修复不受影响。
在大鼠颈动脉损伤模型中，RPM-FG 的周向给药有助于抑制 IH，同时不影响再内皮化。此外，FG 为开发安全、有效、微创的血管周围药物输送方法治疗血管疾病提供了有前景的平台。
