Objective: The pharmacological treatment of cerebral vasospasm (CVS) now includes the experimental use of controlled-release biocompatible compounds that deliver a desired drug locally into the subarachnoid space. A controlled-release system consists of an active material that is incorporated into a carrier, usually in the form of a pellet or a gel. With such systems, the desired agent is delivered slowly and continuously, for long periods of time, directly to the desired site. This technology makes it possible to achieve high local concentrations of therapeutic agents while minimizing systemic toxicity and circumventing the need to cross the blood-brain barrier. This review describes controlled-release systems developed to date for local drug delivery in the treatment of CVS in both animal models and humans.
Methods: A MEDLINE PubMed database search was performed for articles published from 1975 to 2007 with the following search topics: "controlled-release system/polymer," "controlled-release implants," "cerebral vasospasm," "subarachnoid hemorrhage," "subarachnoid space," and "intracranial drug delivery."
Results: Over the past several decades, several controlled-release systems (lactic/ glycolic acid pellets, ethylene vinyl acetate copolymer, liposomes, silicone elastomers) have been developed to deliver various pharmacological agents (papaverine, nicardipine, ibuprofen, nitric oxide donor, calcitonin gene-related peptide, fasudil, recombinant tissue plasminogen activator) intracranially to treat subarachnoid hemorrhage in animal models (rats, rabbits, dogs, and primates). Animal studies have shown promising results, and the few human studies that have been published using controlled-release systems with papaverine or nicardipine report similarly encouraging outcomes.
Conclusion: Controlled-release systems have evolved over the past few years and have been shown experimentally to be an effective strategy for the local delivery of drugs to treat CVS.