The blood–brain barrier (BBB) prevents the brain uptake of most pharmaceuticals. This property arises from the epithelial-like tight junctions within the brain capillary endothelium. The BBB is anatomically and functionally distinct from the blood–cerebrospinal fluid barrier at the choroid plexus. Certain small molecule drugs may cross the BBB via lipid-mediated free diffusion, providing the drug has a molecular weight <400 Da and forms <8 hydrogen bonds. These chemical properties are lacking in the majority of small molecule drugs, and all large molecule drugs. Nevertheless, drugs can be reengineered for BBB transport, based on the knowledge of the endogenous transport systems within the BBB. Small molecule drugs can be synthesized that access carrier-mediated transport (CMT) systems within the BBB. Large molecule drugs can be reengineered with molecular Trojan horse delivery systems to access receptor-mediated transport (RMT) systems within the BBB. Peptide and antisense radiopharmaceuticals are made brain-penetrating with the combined use of RMT-based delivery systems and avidin–biotin technology. Knowledge on the endogenous CMT and RMT systems expressed at the BBB enable new solutions to the problem of BBB drug transport.

https://journals.sagepub.com/doi/pdf/10.1038/jcbfm.2012.126

Drug transport across the blood-brain barrier.

Blood-brain barrier delivery.

Intranasal delivery to the central nervous system: Mechanisms and experimental considerations

Nasal drug delivery--possibilities, problems and solutions.

Polysaccharide hydrogels for modified release formulations.

Purpose. The aim of the study was to investigate whetherdopamine is transferred along the olfactory pathway to the brain followingnasal administration to mice.

Transfer of dopamine in the olfactory pathway following nasal administration in mice

Levels of dopamine in blood and brain following nasal administration to rats

Transfer of morphine along the olfactory pathway to the central nervous system after nasal administration to rodents

Nasal administration of a 3 kDa fluorescein dextran (FD3) solution to rats resulted in transcellular absorption across the olfactory epithelium and transfer to the olfactory bulb within 15 min. After entering the lamina propria, FD3 was transferred in the connective tissue surrounding the olfactory nerve bundles to the olfactory bulb of the brain. More FD3 was absorbed across the olfactory epithelium than across the respiratory epithelium and to the nasal associated lymphoid tissue. Further, the amount of FD3 crossing the olfactory epithelium was region-dependent, with higher amounts absorbed in the turbinates than in the nasal septum. Plastic embedding and sectioning followed by fluorescence microscopy, enabled simultaneous visualization of FD3 in the mucosa and olfactory bulb, as well as the opportunity to store the tissue blocks for a prolonged period of time.

Björn Jansson

Papers

Transfer of dopamine in the olfactory pathway following nasal administration in mice

Levels of dopamine in blood and brain following nasal administration to rats

Transfer of morphine along the olfactory pathway to the central nervous system after nasal administration to rodents

Visualization of in vivo olfactory uptake and transfer using fluorescein dextran.

The influence of gellan gum on the transfer of fluorescein dextran across rat nasal epithelium in vivo.