Development of nicardipine prolonged-release implants after clipping for preventing cerebral vasospasm: from...

We have developed a drug delivery system using a vasodilating drug that can be implanted intracranially at the time of surgery for aneurysm clipping, without systemic side effects or side effects associated with long-term intrathecal drug administration. We started our project on 1994 for making a slowly releasing drug delivery system in vitro because cerebral vasospasm occurs 4-14 days following subarachnoid hemorrhage (SAH). A rod-shaped pellet containing 1 mg of nicardipine for animal study was prepared by heat compression. We presented the efficacy and safety of this drug delivery system using both canine double-hemorrhage and clot placement models. Since October 1999, nicardipine prolonged-release implants (NPRIs) containing 4 mg of nicardipine have been used to prevent vasospasm in patients with SAH. NPRIs were placed in the cistern of the cerebral arteries, where thick clots existed; therefore, vasospasm related to delayed ischemic neurological deficits (DINDs) was highly probable. Vasospasm was completely prevented in the arteries by placing NPRIs adjacent to the arteries during surgery. No complications were experienced. We have performed three studies (a single-center study with consecutive patients; a single-center, randomized, double-blind trial; and a multicenter cooperative study) and have proved that implantation of NPRIs reduces the incidence of cerebral vasospasm and DINDs and improves clinical outcome after SAH.