Local Infusing Antiplatelet Microspheres to Prevent Thrombosis Post-PCI: a Feasibility Study in Rabbit Aorta.

IF 2.5 4区 医学 Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
Yueyou Peng, Kunkun Liu, Wei Tian, Tianfeng Shi, Qixiong Lin, Yanmei Tian, Rongrong Li, Yanfeng Meng
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Abstract

Purpose: After percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT) is required to prevent thrombosis, but systemic DAPT may increase bleeding risk. This study aimed to develop a new concept of antiplatelet therapy administered via local infusion of PLGA-Fe3O4-ticagrelor microspheres (PFTm).

Procedures: PLGA loaded with Fe3O4 and ticagrelor magnetic microspheres were constructed. In vitro study, the morphology, relaxation rate, drug release rate, encapsulation efficiency, and biocompatibility of PFTm were evaluated. In vivo study, vascular injury model of rabbit abdominal aorta was established by Fogarty balloon. The injured rabbit aorta wall was infused PFTm by infusion balloon in the local PFTm therapy group, while the rabbit was injected PFTm intravenously in the systemic PFTm therapy group. The non-therapy control group and healthy control group did not receive PFTm treatment. MR T2WI was performed pre-operation, post-operation to detect PFTm distribution. Then, the targeted abdominal aorta segments were harvest for pathological examination.

Results: The PFTm was spherical with a size of 930.5 ± 134 nm and SPAN was 0.35. The ticagrelor encapsulation efficiency was 82% ± 2%, and the release rate reached 88% ± 2% within 96 h. The r2 of the PFTm was 332.0 mM-1 s-1. All rabbits were successfully established abdominal aorta injury model. MRI showed significant decrease of SNR in aortic wall which represented PFTm infused into aortic wall. Pathology showed that local thrombus was significant inhibited in the local PFTm therapy group compared with the other groups.

Conclusions: The new concept of releasing drugs in a sustained manner for local antiplatelet therapy after PCI was successfully established.

兔主动脉局部灌注抗血小板微球预防pci术后血栓形成的可行性研究。
目的:经皮冠状动脉介入治疗(PCI)后,需要双重抗血小板治疗(DAPT)预防血栓形成,但全身DAPT可能增加出血风险。本研究旨在建立一种通过局部输注plga - fe3o4 -替格瑞洛微球(PFTm)进行抗血小板治疗的新概念。步骤:构建Fe3O4和替格瑞洛磁性微球负载的PLGA。体外实验考察了PFTm的形态、松弛率、药物释放率、包封效率和生物相容性。在体实验中,采用福格蒂球囊法建立兔腹主动脉血管损伤模型。局部PFTm治疗组对损伤兔主动脉壁采用输注球囊输注PFTm,全身PFTm治疗组采用静脉注射PFTm。非治疗对照组和健康对照组均不接受PFTm治疗。术前、术后分别行MR T2WI检查PFTm分布。取目标腹主动脉段进行病理检查。结果:PFTm为球形,尺寸为9305±134 nm, SPAN为0.35。替格瑞洛包封率为82%±2%,96 h内释药率为88%±2%,PFTm的r2为332.0 mM-1 s-1。所有家兔均成功建立腹主动脉损伤模型。MRI显示主动脉壁信噪比明显降低,表明PFTm注入主动脉壁。病理结果显示,局部PFTm治疗组与其他组相比,局部血栓明显受到抑制。结论:成功建立了PCI术后局部抗血小板持续释放的新理念。
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来源期刊
CiteScore
6.90
自引率
3.20%
发文量
95
审稿时长
3 months
期刊介绍: Molecular Imaging and Biology (MIB) invites original contributions (research articles, review articles, commentaries, etc.) on the utilization of molecular imaging (i.e., nuclear imaging, optical imaging, autoradiography and pathology, MRI, MPI, ultrasound imaging, radiomics/genomics etc.) to investigate questions related to biology and health. The objective of MIB is to provide a forum to the discovery of molecular mechanisms of disease through the use of imaging techniques. We aim to investigate the biological nature of disease in patients and establish new molecular imaging diagnostic and therapy procedures. Some areas that are covered are: Preclinical and clinical imaging of macromolecular targets (e.g., genes, receptors, enzymes) involved in significant biological processes. The design, characterization, and study of new molecular imaging probes and contrast agents for the functional interrogation of macromolecular targets. Development and evaluation of imaging systems including instrumentation, image reconstruction algorithms, image analysis, and display. Development of molecular assay approaches leading to quantification of the biological information obtained in molecular imaging. Study of in vivo animal models of disease for the development of new molecular diagnostics and therapeutics. Extension of in vitro and in vivo discoveries using disease models, into well designed clinical research investigations. Clinical molecular imaging involving clinical investigations, clinical trials and medical management or cost-effectiveness studies.
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