Sustained release of papaverine for the treatment of cerebral vasospasm: in vitro evaluation of release kinetics and biological activity

Abstract

Cerebral vasospasm remains an unpredictable and inadequately treated complication of aneurysmal subarachnoid hemorrhage. To date, pharmacological treatment has been plagued in part by an inability to attain sufficiently high concentrations of vasodilator drug in the cerebrospinal fluid without precipitating systemic side effects such as hypotension. To circumvent this limitation of current pharmacological therapy, the authors have developed a sustained-release preparation of papaverine that can be implanted intracranially at the time of surgery for aneurysm clipping. In vitro evaluation of drug-release kinetics has demonstrated that reliable, sustained release of effective amounts of papaverine is possible. An in vitro bioassay using isolated preparations of canine basilar artery has confirmed the biological activity of this preparation. These in vitro studies are described.