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Drug targeting to the brain: Transfer of picolinic acid along the olfactory pathways

Bergstrom, U ; Franzen, A ; Eriksson, C ; Lindh, Christian LU orcid and Brittebo, EB (2002) In Journal of Drug Targeting 10(6). p.469-478
Abstract
Picolinic acid (PA) protects against quinolinic acid- and kainic acid-induced neurotoxicity in the brain. To study the uptake of PA to the brain, we administered [H-3]PA via a unilateral nasal instillation or iv injection to mice. Autoradiography demonstrated a rapid uptake of radioactivity in the olfactory nerve layer and in the ipsilateral olfactory bulb (OB) following nasal instillation of [H-3]PA. After 4h, there was a high level of radioactivity in the central parts of the ipsilateral OB and olfactory peduncle. Moreover, iv injection of [H-3]PA demonstrated a selective uptake and retention of radioactivity in the OB. Gas chromatography-mass spectrometry (GC-MS) demonstrated the presence of PA and PA-glycine conjugate in the OB. In... (More)
Picolinic acid (PA) protects against quinolinic acid- and kainic acid-induced neurotoxicity in the brain. To study the uptake of PA to the brain, we administered [H-3]PA via a unilateral nasal instillation or iv injection to mice. Autoradiography demonstrated a rapid uptake of radioactivity in the olfactory nerve layer and in the ipsilateral olfactory bulb (OB) following nasal instillation of [H-3]PA. After 4h, there was a high level of radioactivity in the central parts of the ipsilateral OB and olfactory peduncle. Moreover, iv injection of [H-3]PA demonstrated a selective uptake and retention of radioactivity in the OB. Gas chromatography-mass spectrometry (GC-MS) demonstrated the presence of PA and PA-glycine conjugate in the OB. In mice with reduced peripheral olfactory innervations there was a decreased uptake of [H-3]PA in the OB as compared to controls suggesting that an intact olfactory neuroepithelium, is a prerequisite for an uptake of PA to the OB. There is an increased interest in brain targeting of drugs with limited ability to pass the blood-brain barrier. The present results demonstrate that PA fulfils structural requirements for a transfer along the olfactory pathways to the brain. (Less)
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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
olfactory system, picolinic acid, intranasal instillation, autoradiography
in
Journal of Drug Targeting
volume
10
issue
6
pages
469 - 478
publisher
Taylor & Francis
external identifiers
  • pmid:12575737
  • wos:000178945600005
  • scopus:0036709519
ISSN
1061-186X
DOI
10.1080/1061186021000038346
language
English
LU publication?
yes
id
79bbf7cd-0365-4e00-8cc8-ae2c82e1e77e (old id 324467)
date added to LUP
2016-04-01 16:35:04
date last changed
2022-02-27 22:12:36
@article{79bbf7cd-0365-4e00-8cc8-ae2c82e1e77e,
  abstract     = {{Picolinic acid (PA) protects against quinolinic acid- and kainic acid-induced neurotoxicity in the brain. To study the uptake of PA to the brain, we administered [H-3]PA via a unilateral nasal instillation or iv injection to mice. Autoradiography demonstrated a rapid uptake of radioactivity in the olfactory nerve layer and in the ipsilateral olfactory bulb (OB) following nasal instillation of [H-3]PA. After 4h, there was a high level of radioactivity in the central parts of the ipsilateral OB and olfactory peduncle. Moreover, iv injection of [H-3]PA demonstrated a selective uptake and retention of radioactivity in the OB. Gas chromatography-mass spectrometry (GC-MS) demonstrated the presence of PA and PA-glycine conjugate in the OB. In mice with reduced peripheral olfactory innervations there was a decreased uptake of [H-3]PA in the OB as compared to controls suggesting that an intact olfactory neuroepithelium, is a prerequisite for an uptake of PA to the OB. There is an increased interest in brain targeting of drugs with limited ability to pass the blood-brain barrier. The present results demonstrate that PA fulfils structural requirements for a transfer along the olfactory pathways to the brain.}},
  author       = {{Bergstrom, U and Franzen, A and Eriksson, C and Lindh, Christian and Brittebo, EB}},
  issn         = {{1061-186X}},
  keywords     = {{olfactory system; picolinic acid; intranasal instillation; autoradiography}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{469--478}},
  publisher    = {{Taylor & Francis}},
  series       = {{Journal of Drug Targeting}},
  title        = {{Drug targeting to the brain: Transfer of picolinic acid along the olfactory pathways}},
  url          = {{http://dx.doi.org/10.1080/1061186021000038346}},
  doi          = {{10.1080/1061186021000038346}},
  volume       = {{10}},
  year         = {{2002}},
}