Biomaterials and the Central Nervous System: Neurosurgical Applications of Materials Science - Biomaterials Science: An Integrated Clinical and Engineering Approach - page 140

effect in a rodent model [33, 34]. Animals had a more rapid onset of anesthesia
and likely achieved less systemic exposure of these opiod agents [33, 34].
While strategies to improve the systemic administration of CNS drugs have
been promising, patients are still exposed to potential side effects from non-
specific drug delivery. To address this limitation, several groups have explored
strategies for delivering pharmacologic agents locally, within the brain. Most
efforts have focused on the treatment of brain tumors, since chemothera-
peutic agents often cause significant side effects, such as bone marrow sup-
pression, nausea, and alopecia. Polymers that have been used intracranially
include polylactide (PL), polyglycolide (PG), copolymers of lactide/glycolide
(PLGA), and polyanhydride poly-bis-propane-sebacic acid (PCPP:SA). All of
these polymers have been safely implanted intracranially and have demon-
strated good biocompatibility and long-term drug release [35]. Gliadel ® is a
polymer-chemotherapy composite wafer approved for intracranial implan-
tation for recurrent glioma tumors and has been demonstrated to be safe
and non-immunogenic when administered intracranially [35] (Figure 6.2).
Unfortunately, increases in survival in patients who have been treated with
Gliadel ® have been modest at best, with survival improved on the order of
months [36]. Some have postulated that these modest increases in survival
are due to inferior tumoricidal activity of carmustine (BCNU), the chemother-
apy in Gliadel ® , or perhaps to the low drug payload achieved in these wafers.
Others have suggested that the tumor target is not appropriate for intracra-
nial implantation, as high-grade glioma tumors are diffuse and infiltrative by
nature. However, in spite of these limitations, the addition of Gliadel ® to the
neurooncology armamentarium has been significant as it has demonstrated
that high concentrations of chemotherapy may be delivered intracranially
and that such concentrations may be well tolerated and efficacious.
FIGuRE 6.2
(a) GLIADEL ® Wafer (polifeprosan 20 with carmustine implant) is a registered trademark of
Eisai Inc. GL188R1 © 2010 Eisai Inc. All rights reserved. September 2010. (b) Gliadel Wafers
being implanted in the brain. (Courtesy of NCI 1997)