title: Delivery of a lactose derivative of endomorphin 1 to the brain via the olfactory epithelial pathway.
abstract: The rapid and direct delivery of a neuroactive endomorphin 1 derivative to the brain via nasal delivery is reported. A synthetic derivative of the native opioid peptide, endomorphin 1 bearing a lactose unit on the N-terminus of the peptide has been previously reported to exhibit antinoceceptive activity similar to morphine after both intravenous and oral administration. This compound has been administered nasally to rats and appeared in the olfactory bulb within 10 min of administration with negligible levels appearing in the circulating blood or in the rest of the brain. These results indicate that the peptide is absorbed into the brain via the olfactory epithelial pathway suggesting nasal delivery may be a viable alternative route of delivery in clinical applications.
authors: School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Brisbane 4072, Australia.
authors: Cécile D
authors: CD
authors: Cros
authors: School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Brisbane 4072, Australia; School of Pharmacy, University of Queensland, St. Lucia, Brisbane 4072, Australia.
authors: Istvan
authors: I
authors: Toth
authors: School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Brisbane 4072, Australia. Electronic address: j.blanchfield@uq.edu.au.
authors: Joanne T
authors: JT
authors: Blanchfield
mesh_terms: D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007785:Lactose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D009294:Narcotics / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D009830:Olfactory Bulb / Q000378:metabolism; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D009294:Narcotics; D009842:Oligopeptides; C105293:endomorphin 1; D007785:Lactose
keywords: Endomorphin-1; Lactose; Nasal drug delivery; Peptide drug delivery