Transfer of Some Carboxylic Acids in the Olfactory System Following Intranasal Administration

Abstract

The uptake of [14C]benzoic acid, 4-chloro[14C]benzoic acid, [3H]phthalic acid and [14C]salicylic acid in the nasal passages and brain was determined following a unilateral intranasal instillation in mice. An uptake of radioactivity from the nasal mucosa to the ipsilateral olfactory bulb was observed up to 4 h after administration following intranasal instillation of these carboxylic acids whereas the level was low in the contralateral olfactory bulb. Autoradiography of mice given [14C]benzoic acid and [14C]salicylic acid by intranasal instillation showed a preferential localization of radioactivity in the axonal and glomerular layer of the olfactory bulb 1 h after the administration. Four hours after administration the radioactivity was present as a gradient from the axonal layer towards the center of the olfactory bulb. Pretreatment of mice with a compound known to damage the olfactory neuroepithelium resulted in a decreased uptake of [14C]benzoic acid in the olfactory bulb. Thin layer chromatography of supernatants from the ipsilateral olfactory bulbs of mice given [14C]benzoic acid by nasal instillation indicated that the radioactivity in the bulbs represented unchanged compound. These results suggest that there is a transfer of some aromatic carboxylic acids in the olfactory pathways.

Evaluation of Direct Transport Pathways of Glycine Receptor Antagonists and an Angiotensin Antagonist from the Nasal Cavity to the Central Nervous System in the Rat Model

“…It is reasonable to assume that molecules are able to utilise both transport pathways simultaneously. Eriksson et al have investigated the distribution of four carboxylic acids following intranasal administration (20). Autoradiography showed that the test substances were distributed throughout the olfactory nerve apparatus and the glomerular layer (outer layer) of the olfactory lobes at 0.5-4 h post-dose.…”

“…Dosing and subsequent sacrifice of each rat was staggered to allow prompt removal of the olfactory lobes and brain in a consistent manner. Blood samples (150-200 μl) were taken via the carotid cannula pre-dose and at 0 (immediately post-dose), 1, 2, 3,5,7,8,9,10,11,15,20,25 and 30 min post-dose.…”

The biocontaminants and complexity of damp indoor spaces: more than what meets the eyes

“…Also, lipopolysaccharides enhance the hepatoxicity of aflatoxin B1 in rats (Barton et al, 2001;Luyendyk et al, 2002Luyendyk et al, , 2003. Finally, C-14 aromatic carboxylic acids are transferred unchanged into the brain and olfactory bulbs following intranasal instillation in mice (Eriksson et al, 1999). These observations point towards at least one probable mechanism for the encephalopathy observed in humans exposed to the biocontaminants in damp indoor spaces.…”

Brain targeting by intranasal drug delivery (INDD): a combined effect of trans-neural and para-neuronal pathway

“…To date, lot of work has been reported for brain targeting using intanasal route (Mathison et al, 1998;Stevens et al, 2011). Few of them include nerve growth factor (Chou & Donovan, 1998), inorganic mercury (Henriksson & Tjalve, 1998), dihydroergotamine (Wang et al, 1998), taurine (Brittebo & Eriksson, 1995), carboxylic acids (Eriksson et al, 1999), 2 0 ,3 0 -didehydro-3 0 -deoxythymidine (Yajima et al, 1998) and many high molecular weight peptides (Frey et al, 1997) bagged in INDD. Kumar et al (1982) who showed that progesterone (MW 314.46 Da) achieved a higher distribution in the CSF than in the blood after intranasal administration.…”