Physicochemical and physiological considerations for efficient nose-to-brain targeting

Introduction: Nasal drug delivery that exploits the olfactory and trigeminal neuronal pathways to deliver drugs to the brain is being widely explored by pharmaceutical companies, for the delivery of challenging drugs. Low-molecular-weight and lipophilic drugs are effectively absorbed by the intranasal route for efficacious brain targeting; however, high-molecular-weight and hydrophilic drugs present challenges in intranasal delivery. Areas covered: The present review critically evaluates the physicochemical properties of drugs and formulation variables that influence brain targeting by the intranasal route. It also encompasses the influence of physiological factors of the nose that can influence absorption and the strategies utilized to increase nasal drug absorption. Expert opinion: The challenges of drug delivery to the brain can be overcome by chemical and pharmaceutical approaches; current research is focused on developing novel drug delivery systems for both local and systemic actions. Nose-to-brain targeting has vast potential for commercialization, as these systems allow the lowering of doses, by direct targeting of the active molecule that provides easy attainment of the effective concentration at the target site. Consequently, these systems are being explored for the delivery of biologically active molecules, to treat the ailments of the CNS and various proteins, amino acids and hormones.