Silk Embolic Material for Catheter-directed Endovascular Drug Delivery.

Abstract

Embolization is a catheter-based minimally invasive procedure that deliberately occludes diseased blood vessels for treatment purposes. We report a novel silk based embolic material (SEM) that was developed and optimized to provide tandem integration of both embolization and the delivery of therapeutics. Natural silk was processed into fibroin proteins of varying lengths and combined with charged nanoclay particles to allow visibility and injectability using clinical catheters as small as 600 microns in diameter at lengths >100\xa0cm.\xa0SEMs loaded with fluorochrome labeled bovine albumin and Nivolumab, which is among the most used immunotherapy drugs world-wide, demonstrated a sustained release profile in vitro over 28 days. In a porcine renal survival model, SEMs with labeled albumin and Nivolumab successfully embolized porcine arteries without recanalization and led to the delivery of both albumin and Nivolumab into the interstitial space of the renal cortex. Mechanistically, we show that tissue delivery is most optimal when the internal elastic membrane of the embolized artery is disrupted. SEM is a potential next-generation multifunctional embolic agent that can achieve embolization and deliver a wide range of therapeutics to treat vascular diseases including tumors. This article is protected by copyright. All rights reserved.