Novel technologies for antiangiogenic drug delivery in the brain.
Antiangiogenic therapies aimed at inhibiting the formation of tumor vasculature hold great promise for cancer therapy, with multiple compounds currently undergoing clinical trials. As with many forms of chemotherapy, antiangiogenic drugs face numerous hurdles in their translation to clinical use. Many such promising agents exhibit a short half-life, low solubility, poor bioavailability and multiple toxic side effects. Furthermore, when targeting malignant brain tumors the blood-brain barrier represents a formidable obstacle, preventing drugs from penetrating into the central nervous system (CNS). In this review, we discuss several preclinical antiangiogenic therapies and describe issues related to the unique conditions in the brain with regard to cancer treatment and neurotoxicity. We focus on the limitations of antiangiogenic drugs in the brain, along with numerous solutions that involve novel biomaterials and nanotechnological approaches. We also discuss an example in which modifying the properties of an antiangiogenic compound enhanced its clinical efficacy in treating tumors while simultaneously mitigating undesirable neurological side-effects.
Benny
Ofra
O
Department of Surgery, Children's Hospital Boston, Harvard Medical School, MA, USA. Ofra.BennyRatsaby@childrens.harvard.edu
Pakneshan
Pouya
P
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy; D016503:Drug Delivery Systems; D005910:Glioma / Q000098:blood supply / Q000188:drug therapy; D006801:Humans; D053758:Nanoparticles
D020533:Angiogenesis Inhibitors