Brain uptake and distribution patterns of 2-hydroxypropyl-ß-cyclodextrin after intrathecal and intranasal administration.
J Pharm Pharmacol
; 74(8): 1152-1159, 2022 Aug 19.
Article
em En
| MEDLINE
| ID: mdl-35596793
ABSTRACT
OBJECTIVES:
Cyclodextrins are increasingly used therapeutically. For example, 2-hydroxypropyl-ß-cyclodextrin (kleptose) is used for the treatment of Niemann-Pick disease. Kleptose crosses the blood-brain barrier poorly, in part because of a central nervous system (CNS)-to-blood (efflux) transporter, and so is administered by the intrathecal (IT) route in the treatment of Niemann-Pick disease.METHODS:
Here, we evaluated the uptake and distribution of kleptose by the brain and spinal cord after intranasal (IN) or IT delivery. KEYFINDINGS:
Kleptose distributed to all regions of the brain and spinal cord after IN administration, with only 3.27% of the administered dose entering the bloodstream. Intrathecal delivery produced levels in the whole brain about 40 times higher than intranasal administration and about 20 times higher than previously found after intravenous administration. About 70-90% of the IT dose rapidly entered the bloodstream, in part because of the previously described efflux transporter. The uptake by CNS after IN and IT was both non-saturable. The uptake by the olfactory bulb, hypothalamus and pons-medulla was favoured by all routes of administration.CONCLUSIONS:
Kleptose was taken up by all regions of the CNS after either IN or IT administration, but IN administration resulted in only a fraction of the uptake of the IT route.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doenças de Niemann-Pick
/
Ciclodextrinas
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article