Je. Eyles et al., Tissue distribution of radioactivity following intranasal administration of radioactive microspheres, J PHARM PHA, 53(5), 2001, pp. 601-607
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.