Optimization of Novel Thermo-gelling Tri-block Co-polymeric Carriers for the Delivery of Paclitaxel for the Treatment Glioblastoma Multiforme
No Access Until
Permanent Link(s)
Other Titles
Author(s)
Abstract
Glioblastoma multiforme (GBM) is the most aggressive primary brain cancer in adults and unfortunately, characterized by a poor prognosis. Standard treatments like surgical resection and chemotherapy are marginally effective. Despite aggressive therapy, the disease ultimately recurs. Local control-released chemotherapy may be administered via carmustine (BCNU) polymer-loaded biodegradable wafers (Gliadel® wafers) to the cavity upon surgical resection. One significant limitation of this modality is the instability of BCNU in aqueous media. Moreover, the effective therapeutic distance of the wafers extends only a few millimeters from the resection cavity, while recurrences occur often centimeters away. New carriers and pharmacological agents are being actively explored. One such carrier is derived from a novel set of poly(DL-lactide-co-glycolide-b–ethylene glycol-b-DL-lactide-co-glycolide) (PLGA-PEG-PLGA) thermo-gelling tri-block copolymers capable of sustained release of paclitaxel. Paclitaxel has been shown in vitro and in vivo to be effective against glioma cells while having a much slower degradation rate than carmustine; this slower degradation rate may allow deeper penetration into the brain, and as a result, effective concentrations can be sustained for longer periods. We seek to test whether thermo-gelling hydrogel carriers of paclitaxel could result in novel therapies for the treatment of GBM. We also seek to optimize the configuration of the thermo-gelling hydrogels within the resection cavity to maximize drug delivery to the surrounding brain.