Perivascular application of sirolimus multilayer nanofibrous mat for prevention of vascular stenosis: Preparation, In vitro characterization, and In vivo efficacy evaluation

Abstract

Graft stenosis, occurring after coronary artery bypass surgery (CABG), diminishes the efficacy and long-term patency of vascular interventions. Multilayer nanofibers (NFs) are developed to provide localized controlled release of sirolimus to prevent vascular stenosis, as well as limit drug exposure to other organs. NFs are composed of a mid-layer of drug and polycaprolactone (PCL), a bioadhesive layer of PCL and collagen, and a backing layer of PCL. NFs are characterized in vitro regarding morphology, mechanical strength, contact angle, water uptake, drug content, and drug release behavior. The average fiber diameter is around 300–500 nm. Sirolimus entrapment is confirmed by drug content, FTIR, and XRD. It is found that sirolimus is released from multilayer NFs in a sustained manner with about half of the payload released over one week. Sirolimus multilayer NFs are implanted in the rat carotid artery after inducing vascular injury. Histological, immunohistochemical (α-SMA, Ki-67, and CD31), and in vivo imaging analyses reveal that the administration of sirolimus multilayer NFs causes significant inhibition of intimal hyperplasia in the rat carotid injury model compared to the control groups and drug suspension. The obtained results reveal that the sirolimus multilayer nanosystem could be a promising carrier for local vascular drug delivery.