Introduction: Implanted drug delivery systems offer many advantages compared to oral or injection methods, including ease of concentration maintenance in a narrow therapeutic window, consistent local drug delivery to difficult locations, and decreased systemic toxicity. While drug eluting materials are the most common system today (e.g. Gliadel), they are limited in their inability to release a complex combination of multiple drugs, on demand, and after a delay.
In this project, we engineered intracranially-implantable microchips that overcame these limitations. These microchips had 3 membranes that could be opened independently by applying electric current: opening more membranes resulted in faster drug delivery. In addition to examining the kinetics and timing of drug release, we also compared the efficacy of microchip to polymer-based drug delivery.
Methods: Sixty-four rats were divided into 8 groups: no-treatment, unactivated-device, 2 5-mg temozolomide wafers implanted on day 5, 3m/0d (a microchip with 3 membranes opened on day 0), 3m/3d, 3m/5d, 2m/0d, and 1m/0d. All rats were implanted with intracranial 9L gliosarcoma and/or a microchip containing 10-mg temozolomide on day 0.
Results: Control animals and animals with unactivated microchips had median survivals of 14 and 17 days, respectively. Rats with 3 membranes activated on day 0, 3, and 5 had median survivals of 41, 25, and 24 days. Rats with 3, 2, and 1 membranes activated on day 0 had median survivals of 41, 29, and 22 days. The rats with 2 temozolomide wafers implanted on day 5 had median survival of 35 days.
Conclusions: Our results show that releasing drugs earlier and faster resulted in improved median survival. The polymer wafers resulted in better survival, most likely because they were able to release drug omni-directionally. In conclusion, we have demonstrated a successful microchip-based intracranial drug-delivery system.
Patient Care: Our results show that releasing drugs earlier and faster resulted in improved median survival. The polymer wafers resulted in better survival, most likely because they were able to release drug omni-directionally. These results are preclinical data that could lead to future improved outcomes in patients with GBMs.
Learning Objectives: The reader should learn that microchips may prove to be a viable option for intracranial delivery for the treament of brain tumors.