title: Tissue distribution of radioactivity following intranasal administration of radioactive microspheres.
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.
authors.affiliation: Pharmaceutical Sciences, Life and Health Sciences, Aston University, Birmingham, UK.
authors.forename: J E
authors.initials: JE
authors.lastname: Eyles
authors.forename: I D
authors.initials: ID
authors.lastname: Spiers
authors.forename: E D
authors.initials: ED
authors.lastname: Williamson
authors.forename: H O
authors.initials: HO
authors.lastname: Alpar
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000941:Antigens / Q000032:analysis; D005260:Female; D007700:Kinetics; D008099:Liver / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D009296:Nasal Cavity; D011137:Polystyrenes / Q000493:pharmacokinetics*; D012538:Scandium; D013154:Spleen / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D000941:Antigens; D011137:Polystyrenes; C003771:Amberlite XAD-2 resin; D012538:Scandium