Formulation and Physiological Factors Influencing CNS Delivery upon Intranasal Administration

The treatment of central nervous system (CNS) disorders is particularly challenging because of a variety of formidable barriers to effective and persistent delivery of therapeutic compounds. This review discusses the potential of intranasal drug administration as a means to bypass a major barrier, the blood-brain barrier, and allow for direct delivery of drugs into the CNS. The article emphasizes physicochemical properties of intranasal drug formulations as well as relevant anatomical and physiological factors in intranasal delivery of drugs for CNS therapy. Published examples of intranasal administration of small molecular weight drugs, peptides and proteins, and novel formulations for delivering a broad spectrum of molecules are discussed. Finally, the article provides several strategies for effectively enhancing nose-to-brain transport of drug molecules through rational formulation design and optimization.