Cerebrovascular Section Best Basic Scientific Paper Abstract Award - A Drug-Loaded Flow Diverting Stent for Delivery of Gene Therapy to Intracranial Aneurysms

Introduction: Advances and new techniques in endovascular neurosurgery have revolutionized the safety of treating intracranial aneurysms (IAs). However, a significant proportion of IAs treated with endovascular devices still recur. There remains a need to develop new, personalized therapeutics to improve outcomes for these patients. To this end, there has been intensified effort in the field to identify specific molecular pathways as drivers of IA pathogenesis and gain insight into potential therapeutic targets. Recently, activating somatic variants in the platelet-derived growth factor beta (PDGFRB) gene have been identified as drivers of IAs, particularly among fusiform IAs. In fact, several studies have shown that this pathogenesis can be reversed using chemotherapies that inhibit PDGFRB, such as sunitinib. To achieve targeted delivery of sunitinib to the IA tissue and prevent toxic side effects associated with the chemotherapy, we propose a system for local delivery of sunitinib along the surface of a flow diverting stent (FDS).

Methods: FDS were coated with biodegradable polymers embedded with sunitinib. Surface characterization was performed to assess the stability of the coating. Elution of the sunitinib from the stent submerged into a phosphate buffered saline (PBS) solution was quantified using adsorption at 400 nm over a period of 21 days.

Results: Surface characterization confirmed the stability and uniformity of the sunitinib-embedded polymer coating on the stent. Progressive elution of the sunitinib from the surface of the stent was observed over an initial period of 21 days.

Conclusion : Here, we show the ability to load a gene therapy for delivery to IAs along the surface of a stent. We also show early evidence of elution of the drug from the stent surface. Future work will focus on longer-term (1 month) release both in a static medium as well as in an in vitro flow model of a candidate aneurysm.