Tissue distribution of radioactivity following intranasal administration of radioactive microspheres

被引:41
作者
Eyles, JE
Spiers, ID
Williamson, ED
Alpar, HO [1 ]
机构
[1] Aston Univ, Birmingham B4 7ET, W Midlands, England
[2] DERA, Chem & Biol Defence Sector, Salisbury SP4 0JQ, Wilts, England
关键词
D O I
10.1211/0022357011775929
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 styrenedivinyl benzene 7-mum-diameter microspheres. Groups of BALB/c mice received 0.250 mg (47.5 kBq) particles suspended in either 50-muL or 10-muL 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 muL) administration vehicle volumes resulted in substantial bronchopulmonary deposition (similar to 50 % of administered dose). Intranasal instillation of microspheres suspended in 10-muL 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-muL volume particle suspension nasally, accumulation of potentially relevant quantities of radioactivity 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 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.
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页码:601 / 607
页数:7
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