|Title||Relative vascular permeability and vascularity across different regions of the rat nasal mucosa: implications for nasal physiology and drug delivery.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Kumar NN, Gautam M, Lochhead JJ, Wolak DJ, Ithapu V, Singh V, Thorne RG|
|Date Published||2016 Aug 25|
Intranasal administration provides a non-invasive drug delivery route that has been proposed to target macromolecules either to the brain via direct extracellular cranial nerve-associated pathways or to the periphery via absorption into the systemic circulation. Delivering drugs to nasal regions that have lower vascular density and/or permeability may allow more drug to access the extracellular cranial nerve-associated pathways and therefore favor delivery to the brain. However, relative vascular permeabilities of the different nasal mucosal sites have not yet been reported. Here, we determined that the relative capillary permeability to hydrophilic macromolecule tracers is significantly greater in nasal respiratory regions than in olfactory regions. Mean capillary density in the nasal mucosa was also approximately 5-fold higher in nasal respiratory regions than in olfactory regions. Applying capillary pore theory and normalization to our permeability data yielded mean pore diameter estimates ranging from 13-17 nm for the nasal respiratory vasculature compared to <10 nm for the vasculature in olfactory regions. The results suggest lymphatic drainage for CNS immune responses may be favored in olfactory regions due to relatively lower clearance to the bloodstream. Lower blood clearance may also provide a reason to target the olfactory area for drug delivery to the brain.
|Alternate Journal||Sci Rep|
|PubMed Central ID||PMC4997340|
|Grant List||KL2 TR000428 / TR / NCATS NIH HHS / United States |
T32 EB011434 / EB / NIBIB NIH HHS / United States
UL1 RR025011 / RR / NCRR NIH HHS / United States
UL1 TR000427 / TR / NCATS NIH HHS / United States
Relative vascular permeability and vascularity across different regions of the rat nasal mucosa: implications for nasal physiology and drug delivery.
Faculty Member Reference:
Jeffrey J. Lochhead, PhD