Coil and flow diverting stents as drug delivery platforms for cerebral aneurysm treatment

Abstract

Cerebral aneurysm occlusion with coils and flow diverting stents has become the first line treatment for both unruptured and ruptured cerebral aneurysms. As these technologies have advanced, there have been changes in device shape and surface coating to enhance aneurysm embolization while reducing stent thrombogenicity. Drug eluting stents have been used with great success in the targeted delivery of rapamycin, a mTOR complex 1 inhibitor to prevent restenosis in coronary and peripheral artery disease. However, few studies have investigated the use of coils and stents as delivery platforms for sustained drug release to cerebral aneurysm tissue. In this study, we used the bio-compatible and degradable polymers, gelatin and PLGA and a simple evaporative coating technique to investigate the release of rapamycin over time from coated platinum coils and Pipeline flow diverting stents. Rapamycin coated coils were incubated with human vascular endothelial cells in vitro to confirm therapeutic levels of rapamycin release. The rate of rapamycin release was similar in both gelatin and PLGA coated coils and was sustained for more than three weeks. Rapamycin was bioactive, at a therapeutic dose and inhibited mTOR complex 1 in human brain endothelial cells treated with a rapamycin coated coil. The relative degree of mTOR complex 1 inhibition was greater in PLGA compared to gelatin coated coils. Coating flow diverting stents with a rapamycin-PLGA coating demonstrated continuous rapamycin release over a 35 day period. Reducing the percent PLGA polymer concentration caused a robust and sustainable release of rapamycin. The PLGA coating was resilient enough to allow device recapturing without affecting rapamycin eluting rates or device deployment and expansion. This work provides a simple, feasible and tunable method to coat occlusion devices for preclinical studies investigating targeted drug delivery for improved parent vessel healing and aneurysm obliteration.