ABSTRACT
This chapter reviews the two conceptually different approaches to overcoming the blood-brain barrier and achieving a therapeutic level of an oligodeoxynucleotide (ODN) in the brain or Cerebrospinal fluid. It also discusses what the authors have learned in their laboratory in studies of oligonucleotide administration by continuous infusion into the rat brain. The chapter points out that the blood-brain barrier of a healthy animal is a formidable obstacle to intravenously administered oligonucleotides. It shows that if intravenous administration of oligonucleotides to the central nervous system (CSN) is to work, fairly complex manipulations will be necessary. The chapter focuses on a series of studies on pharmacokinetics of oligonucleotides in a rat CNS model. It explores the direct injection of oligonucleotides into the caudate region of the brain. The chapter suggests that the higher clearance of phosphodiester oligonucleotides reflects their instability. It examines administration of oligonucleotides to growing glioblastoma tumors by continuous infusion.
