2. Academic Validation
  3. Ultrasound-Guided Periadventitial Administration of Rapamycin-Fibrin Glue Attenuates Neointimal Hyperplasia in the Rat Carotid Artery Injury Model

Ultrasound-Guided Periadventitial Administration of Rapamycin-Fibrin Glue Attenuates Neointimal Hyperplasia in the Rat Carotid Artery Injury Model

  • Eur J Pharm Sci. 2023 Oct 16:106610. doi: 10.1016/j.ejps.2023.106610.
Zhentao Qiao 1,  Fuhang Wang 2,  Dongjian Han 2,  Yuansong Zhuang 2,  Qingjiao Jiang 2,  Yi Zhang 2,  Miaomiao Liu 2,  Quanxu An 2,  Zhiwei Wang 1,  Deliang Shen 3
Affiliations

Affiliations

  • 1 Department of Vascular and Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University.
  • 2 Department of Cardiology, The First Affiliated Hospital of Zhengzhou University.
  • 3 Department of Cardiology, The First Affiliated Hospital of Zhengzhou University. Electronic address: [email protected].
PMID: 37852309 DOI: 10.1016/j.ejps.2023.106610
Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords

Periadventitial; fibrin glue; neointimal hyperplasia; rapamycin; the rat carotid injury model; vascular smooth muscle cells.

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