title: Relative vascular permeability and vascularity across different regions of the rat nasal mucosa: implications for nasal physiology and drug delivery.
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.
authors: Pharmaceutical Sciences Division, University of Wisconsin-Madison School of Pharmacy, Room #5113, Rennebohm hall, 777 Highland avenue, Madison, WI - 53705, USA.
authors: Niyanta N
authors: NN
authors: Kumar
authors: Pharmaceutical Sciences Division, University of Wisconsin-Madison School of Pharmacy, Room #5113, Rennebohm hall, 777 Highland avenue, Madison, WI - 53705, USA.
authors: Mohan
authors: M
authors: Gautam
authors: Pharmaceutical Sciences Division, University of Wisconsin-Madison School of Pharmacy, Room #5113, Rennebohm hall, 777 Highland avenue, Madison, WI - 53705, USA.
authors: Jeffrey J
authors: JJ
authors: Lochhead
authors: Pharmaceutical Sciences Division, University of Wisconsin-Madison School of Pharmacy, Room #5113, Rennebohm hall, 777 Highland avenue, Madison, WI - 53705, USA.|Clinical Neuroengineering Training Program, University of Wisconsin-Madison Biomedical Engineering, Engineering Centers Building, 1550 Engineering Drive, Room #2120, Madison WI - 53706, USA.
authors: Daniel J
authors: DJ
authors: Wolak
authors: Department of Computer Sciences, University of Wisconsin-Madison, 5780 Medical Sciences Center, 1300 University Avenue, Madison, WI - 53706, USA.
authors: Vamsi
authors: V
authors: Ithapu
authors: Department of Computer Sciences, University of Wisconsin-Madison, 5780 Medical Sciences Center, 1300 University Avenue, Madison, WI - 53706, USA.
authors: Vikas
authors: V
authors: Singh
authors: Pharmaceutical Sciences Division, University of Wisconsin-Madison School of Pharmacy, Room #5113, Rennebohm hall, 777 Highland avenue, Madison, WI - 53705, USA.|Clinical Neuroengineering Training Program, University of Wisconsin-Madison Biomedical Engineering, Engineering Centers Building, 1550 Engineering Drive, Room #2120, Madison WI - 53706, USA.|Neuroscience Training Program &Center for Neuroscience, Rooms 9531 &9533, Wisconsin Institutes for Medical Research II, 1111 Highland Ave. Madison, WI - 53705, USA.|Cellular and Molecular Pathology Graduate Training Program, University of Wisconsin-Madison, UW Department of Pathology and Laboratory Medicine 1685 Highland Avenue Madison, WI - 53705, USA.
authors: Robert G
authors: RG
authors: Thorne
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D019540:Area Under Curve; D002199:Capillary Permeability; D004058:Diffusion; D016503:Drug Delivery Systems; D005260:Female; D057446:Hydrodynamics; D008198:Lymph Nodes / Q000378:metabolism; D009297:Nasal Mucosa / Q000098:blood supply* / Q000378:metabolism*; D009831:Olfactory Mucosa / Q000378:metabolism; D061848:Optical Imaging; D004364:Pharmaceutical Preparations / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000737:chemistry; D014966:Xanthenes / Q000737:chemistry
chemical_list: D004364:Pharmaceutical Preparations; D014966:Xanthenes; D012710:Serum Albumin, Bovine; C034657:Texas red