Development of microspheres for neurological disorders: From basics to clinical applications

Drug delivery to the central nervous system remains a challenging area of i nvestigation for both basic and clinical neuroscientists. Numerous drugs ar e generally excluded from blood to blain transfer due to the negligible per meability of the brain capillary endothelial wall, which makes up the blood brain barrier in vivo. For several years, we have explored the potential a pplications of the microencapsulation of therapeutic agents to provide loca l controlled drug release in the central nervous system. Due to their size, these microparticles can be easily implanted by stereotaxy in discreet, pr ecise and functional areas of the brain without damaging the surrounding ti ssue. This type of implantation avoids the inconvenient insertion of large implants by open surgery and can be repeated if necessary. We have establis hed the compatibility of poly(lactide-co-glycolide) microspheres with brain tissues. Presently, the most developed applications concern Neurology and Neuro-oncology, with local delivery of neurotrophic factors and antimitotic drugs into neurodegenerative lesions and brain tumours, respectively. The drugs that had been encapsulated by our group included nerve growth factor (NGF), 5-fluorouracil (5-FU), idoxuridine and BCNU. Preclinical studies hav e been performed with each drug. Studies with NGF are reported as an exampl e. A phase I/II clinical trial has been carried out in patients with newly diagnosed glioblastomas to assess the potentialities of 5-FU-loaded microsp heres when intracranially implanted. (C) 2000 Elsevier Science B.V. All rig hts reserved.