Relative vascular permeability and vascularity across different regions of the rat nasal mucosa: Implications for nasal physiology and drug delivery

Niyanta N. Kumar, Mohan Gautam, Jeffrey J. Lochhead, Daniel J. Wolak, Vamsi Ithapu, Vikas Singh, Robert G. Thorne

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number31732
JournalScientific reports
Volume6
DOIs
StatePublished - Aug 25 2016
Externally publishedYes

ASJC Scopus subject areas

  • General

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