Particulate Drug Carriers to Cerebral Side Aneurysms

Background: Aneurysms are blood filled sac like bulges in the wall of a blood vessel. They commonly develop around blood vessel bifurcations or weakened areas in a blood vessel wall. Cerebral aneurysms develop on the brain vasculature and result in thousands of deaths each year due to aneurysm hemorrhaging. Yet, the available treatment is exclusively invasive including stenting, clipping and coiling which are associated with high rate of complications themselves.From a fluid mechanics point of view, aneurysms are characterized by low shear recirculating flows which have unique mass transport properties allowing micron sized particles to linger in the aneurysm cavity. Furthermore, high rupture risk aneurysms frequently exhibit disrupted endothelium and exposed collagen inside the sac. Utilizing these characteristics, we developed micron sized drug carriers functionalized with platelet Glycoprotein VI (platelet’s collagen membrane receptor) aimed at efficiently homing injured aneurysms.

Methods: To test the targeting efficacy under relevant conditions, we constructed a programmable pulsatile prefusion system to which idealized aneurysm models were connected. The examined models mimic vulnerable aneurysm physiology by being lined with endothelial cells at the parent artery region while the aneurysm cavity was coated with collagen. We then injected Glycoprotein VI coated particles and examined their deposition patterns in the models compared to control particles.

Results: The experimental results show enhanced selective deposition of GPVI micro-particles on collagen coated surfaces within aneurysm cavity.

Conclusion: Our results highlight the potential of functionalized micro-particles for targeted drug delivery to vulnerable aneurysms.

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