Depot delivery of dexamethasone and cediranib for the treatment of brain tumor associated edema in an intracranial rat glioma model.
Treatments of brain tumor associated edema with systemically delivered dexamethasone, the standard of care, and cediranib, a novel anti-edema agent, are associated with systemic toxicities in brain tumor patients. A tunable, reservoir-based drug delivery device was developed to investigate the effects of delivering dexamethasone and cediranib locally in the brain in an intracranial 9L gliosarcoma rat model. Reproducible, sustained releases of both dexamethasone and solid dispersion of cediranib in polyvinylpyrrolidone (AZD/PVP) from these devices were achieved. The water-soluble AZD/PVP, which exhibited similar bioactivity as cediranib, was developed to enhance the release of cediranib from the device. Local and systemic administration of both dexamethasone and cediranib was equally efficacious in alleviating edema but had no effect on tumor growth. Edema reduction led to modest but significant improvement in survival. Local delivery of dexamethasone prevented dexamethasone-induced weight loss, an adverse effect seen in animals treated with systemic dexamethasone. Local deliveries of dexamethasone and cediranib via these devices used only 2.36% and 0.21% of the systemic doses respectively, but achieved similar efficacy as systemic drug deliveries without the side effects associated with systemic administration. Other therapeutic agents targeting brain tumor can be delivered locally in the brain to provide similar improved treatment outcomes.
Harvard-MIT Division of Health Sciences & Technology, Cambridge, MA, USA; The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Qunya
Q
Ong
Neurology, Massachusetts General Hospital, Boston, MA, USA.
Fred H
FH
Hochberg
The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Materials Science & Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: mjcima@mit.edu.
Michael J
MJ
Cima
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000150:complications / Q000188:drug therapy; D002478:Cells, Cultured; D003907:Dexamethasone / Q000008:administration & dosage* / Q000627:therapeutic use; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004487:Edema / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D005910:Glioma / Q000150:complications / Q000188:drug therapy; D061307:Human Umbilical Vein Endothelial Cells; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D011799:Quinazolines / Q000008:administration & dosage* / Q000627:therapeutic use; D011916:Rats, Inbred F344; D007211:Indoles
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D003907:Dexamethasone; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C500926:cediranib; D007211:Indoles
Brain tumor associated edema; Cediranib; Depot; Dexamethasone; Drug delivery