Tissue distribution of radioactivity following intranasal administration of radioactive microspheres

Citation
Je. Eyles et al., Tissue distribution of radioactivity following intranasal administration of radioactive microspheres, J PHARM PHA, 53(5), 2001, pp. 601-607
Citations number
22
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACY AND PHARMACOLOGY
ISSN journal
00223573 → ACNP
Volume
53
Issue
5
Year of publication
2001
Pages
601 - 607
Database
ISI
SICI code
0022-3573(200105)53:5<601:TDORFI>2.0.ZU;2-N
Abstract
The aim of this study was to increase understanding of the kinetics of micr oparticle distribution and elimination following intranasal application. To do this we investigated the in-vivo distribution of radioactivity followin g intranasal instillation of scandium-46 labelled styrenedivinyl benzene 7- mum-diameter microspheres. Groups of BALB/c mice received 0.250 mg (47.5 kB q) particles suspended in either 50-muL or 10-muL Volumes of phosphate buff ered saline. The in-vivo distribution of radioactivity was influenced by th e volume of liquid that was used to instil the microsphere suspension. Comp aratively large (50 muL) administration vehicle volumes resulted in substan tial bronchopulmonary deposition (similar to 50 % of administered dose). In tranasal instillation of microspheres suspended in 10-muL volumes tended to restrict particle deposition initially to the nasal cavity. For both admin istration vehicle volumes tested, the radioactivity per unit mass of excise d nasal-associated lymphoid tissue (NALT) was found to be consistently elev ated relative to other tissues. This corroborates the findings of other wor kers who have previously identified NALT as an active site of microparticle accumulation following intranasal application. Elimination via the aliment ary canal was the principal fate of intranasally applied radiolabelled mate rial. No significant concentration of radioactivity within excised gut-asso ciated lymphoid tissue (GALT) (Peyer's patches) was noted. At latter time p oints we observed, in mice that received the 50-muL volume particle suspens ion nasally, accumulation of potentially relevant quantities of radioactivi ty in the liver (0.3 % after 576 h) a nd 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 com partments than are those mucosae in the gastrointestinal tract or nasophary nx. This effect may contribute to the effectiveness of pulmonary delivered antigen-loaded microparticles as humoral immunogens.