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Preparation and experimental research into retrievable rapamycin- and heparin-coated vena cava filters: a pilot study

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Abstract

The use of retrievable vena cava filters (RVCFs) was once commonplace, but filter retrieval was often very difficult. Most unsuccessful retrieval was due to intimal hyperplasia of the inferior vena cava and in-filter thrombosis. This pilot study aimed to design a drug-eluting RVCF. The hypothesis was that coated drugs could be released continuously to inhibit vena intimal hyperplasia and thrombosis, and thus improve the retrieval rates of RVCFs. Various concentrations of polycaprolactone (PCL)/chloroform solution were made from a mixture of Rapamycin and Heparin according to the quality of PCL. The drug was coated onto the surface of the filters by a process of dipping. In vitro tests were performed to check stability and in vitro drug release. Animals receiving filter implantation were divided into 4 groups, the experimental intervention group (EI), experimental laparotomy group (EL), control intervention group (CI), and control laparotomy group (CL). Filters were retrieved by laparotomy in the EL and CL groups, and by interventional operation in the EI and CI groups at 10, 20 and 30 days after implantation. Pathological endothelia biopsies were performed with wood grain-eosin (HE) staining and immunohistochemical examination, with the proliferating cell nuclear antigen (PCNA) index, and the results were compared between the experimental and control groups. The weight of thrombus within the filters was also measured by scale and compared. The coating concentration that succeeded in completely covering the surface was 0.2 g/ml. There was better coverage by SEM at this concentration, and the coated drugs had no obvious loss after filter release. The drug release curves showed that the amount of Heparin released was more than 50 % at day 1; Rapamycin released little in the first few days, beginning in earnest at 20 to 30 days. The filters were easy to retrieve at 10 days for both groups, while neither could be retrieved at 30 days. However, at 20 days the filter in the EI group could be retrieved with some difficulty, but the filter in the CI group couldn’t be removed at all. The pathological examination and immunohistochemical PCNA examination results showed that the use of drug-eluting filters could effectively inhibit endothelial hyperplasia at 10 and 20 days, but was less effective at 30 days. There was no apparent difference in the total weight of blood clots between the experimental and control groups. We successfully conducted a pilot study into preparing Rapamycin- and Heparin-coated RVCFs. In vitro and in vivo tests further proved the possibility of improving the retrieval rates of RVCFs by effectively inhibiting vein endothelial proliferation, but the anticoagulation and antithrombosis effects of Heparin were unsatisfactory.

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Correspondence to Fuxian Zhang.

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Zhao, H., Zhang, F., Liang, G. et al. Preparation and experimental research into retrievable rapamycin- and heparin-coated vena cava filters: a pilot study. J Thromb Thrombolysis 41, 422–432 (2016). https://doi.org/10.1007/s11239-015-1278-3

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Keywords

  • Retrievable vena cava filter
  • Drug-coating
  • Rapamycin
  • Heparin