Related Experiment Video
Updated: Oct 7, 2026
Novel Methods for Intranasal Administration Under Inhalation Anesthesia to Evaluate Nose-to-Brain Drug Delivery
Published on: November 14, 2018
Tissue distribution of radioactivity following intranasal administration of radioactive microspheres
J E Eyles1, I D Spiers, E D Williamson
1Pharmaceutical Sciences, Life and Health Sciences, Aston University, Birmingham, UK.
Abstract:
The aim of this study was to increase understanding of the kinetics of microparticle distribution and elimination following intranasal application. To do this we investigated the in-vivo distribution of radioactivity following intranasal instillation of scandium-46 labelled styrene-divinyl benzene 7-microm-diameter microspheres. Groups of BALB/c mice received 0.250 mg (47.5 kBq) particles suspended in either 50-microL or 10-microL volumes of phosphate buffered saline. The in-vivo distribution of radioactivity was influenced by the volume of liquid that was used to instil the microsphere suspension. Comparatively large (50 microL) administration vehicle volumes resulted in substantial bronchopulmonary deposition (approximately 50% of administered dose). Intranasal instillation of microspheres suspended in 10-microL volumes tended to restrict particle deposition initially to the nasal cavity. For both administration vehicle volumes tested, the radioactivity per unit mass of excised nasal-associated lymphoid tissue (NALT) was found to be consistently elevated relative to other tissues. This corroborates the findings of other workers who have previously identified NALT as an active site of microparticle accumulation following intranasal application. Elimination via the alimentary canal was the principal fate of intranasally applied radiolabelled material. No significant concentration of radioactivity within excised gut-associated lymphoid tissue (GALT) (Peyer's patches) was noted. At latter time points we observed, in mice that received the 50-microL volume particle suspension nasally, accumulation of potentially relevant quantities of radioactivity in the liver (0.3% after 576 h) and spleen (0.04% after 576 h). Thus, our data corroborate the notion that epithelial membranes in the lung are probably less exclusive to the entry of microparticulates into systemic compartments than are those mucosae in the gastrointestinal tract or nasopharynx. This effect may contribute to the effectiveness of pulmonary delivered antigen-loaded microparticles as humoral immunogens.
Insights
Intranasal microparticle delivery volume impacts distribution. Larger volumes increase lung deposition, while smaller volumes concentrate particles in the nasal cavity, with NALT accumulating the most radioactivity.
Area of Science:
- Pharmacokinetics and Drug Delivery
- Biomedical Engineering
- Immunology
Background:
- Intranasal drug delivery offers a non-invasive route for systemic and local therapeutic administration.
- Understanding microparticle distribution and elimination kinetics is crucial for optimizing intranasal delivery strategies.
- Nasal-associated lymphoid tissue (NALT) is a key immune structure in the nasopharynx, potentially involved in microparticle uptake.
Purpose of the Study:
- To investigate the in-vivo distribution and elimination kinetics of microparticles after intranasal administration.
- To determine the influence of administration vehicle volume on microparticle deposition and translocation.
- To assess the accumulation of microparticles in key lymphoid tissues, including NALT and GALT.
Main Methods:
- Scandium-46 labeled microspheres (7-microm diameter) were administered intranasally to BALB/c mice in 10-microL or 50-microL volumes.
- Radioactivity was measured in various tissues over time to track microparticle distribution and elimination.
- Quantification of radioactivity in excised nasal-associated lymphoid tissue (NALT) and gut-associated lymphoid tissue (GALT) was performed.
Main Results:
- Administration vehicle volume significantly influenced microparticle distribution; 50-microL volumes led to ~50% bronchopulmonary deposition.
- 10-microL volumes restricted initial particle deposition to the nasal cavity.
- Radioactivity per unit mass was consistently elevated in NALT compared to other tissues, irrespective of vehicle volume.
- Elimination primarily occurred via the alimentary canal, with no significant GALT accumulation.
- Late accumulation of radioactivity was observed in the liver and spleen following 50-microL intranasal administration.
Conclusions:
- Epithelial membranes in the lung may be more permeable to microparticulates entering systemic circulation than those in the gastrointestinal tract or nasopharynx.
- The volume of the administration vehicle is a critical factor in controlling microparticle deposition and subsequent distribution after intranasal instillation.
- These findings suggest potential for pulmonary delivery of antigen-loaded microparticles as effective humoral immunogens.
Related Concept Videos
01:25Imaging Studies II: Positron Emission Tomography and Scintigraphy
Fundamental Principles of PET
01:13Radiological Investigation III: Pulmonary Angiogram and PET Scan
Pulmonary Angiogram
A Pulmonary Angiogram is an invasive procedure involving injecting a contrast medium through a catheter threaded into the pulmonary artery or the right side of the heart to visualize the pulmonary vasculature. Computed Tomography (CT) scans have mainly replaced this...