Article (Scientific journals)
Scintigraphic visualization of intrathecal liposome biodistribution.
Umbrain, V; D'Haese, J; Alafandy, M et al.
1997In Acta Anaesthesiologica Scandinavica, 41 (1 Pt 1), p. 25-34
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Keywords :
Animals; Cerebrospinal Fluid/metabolism; Humans; Injections, Spinal; Liposomes/administration & dosage/pharmacokinetics; Particle Size; Rats; Rats, Wistar; Sodium Pertechnetate Tc 99m/diagnostic use; Technetium/diagnostic use; Tissue Distribution
Abstract :
[en] BACKGROUND: Liposomes containing local anaesthetics have been administered intrathecally and in the epidural space. Poor attention has been given to the pharmacokinetics of liposomes as drug carriers. Therefore, we observed the biodistribution of liposomes after intrathecal injection in rats by scintigraphic imaging during 24 h. METHODS: We administered 99mTc-labeled multilamellar (MLV) and small unilamellar vesicles (SUV) of defined size and volume dispersities into the cerebrospinal fluid at the lumbar level. Those vesicles were free of contamination by radiolabeled colloids as visualized by light and electron microscopy and of neurotoxic products from phosphatidylcholine hydrolysis and peroxidation, both during the preparation process and after 24 h incubation in cerebrospinal fluid at 37 degrees C in vitro. RESULTS: SUV immediately diffused from the lumbar site of injection to the head and were cleared between 1 and 24 h after injection. MLV were cleared more slowly from the spinal space and appeared in the head region 1 h after injection where they accumulated up to 24 h. These differences were explained in terms of vesicle sizes and volumes. SUV with 0.05 micron diameters were rapidly absorbed into the blood through the arachnoid granulations. In contrast, particles larger than the upper size limit of the arachnoid granulations permeability (+/- 8 microns) could accumulate in the head with a slow elimination rate. CONCLUSION: This difference in clearance from the intrathecal space outlines the importance of defining the size of the liposomes, the distribution of a tracer or a drug inside the liposomal preparation, the chemical stability and the absence of toxic degradation products of liposome formulations before clinical use.
Disciplines :
General & internal medicine
Author, co-author :
Umbrain, V
D'Haese, J
Alafandy, M
De Roover, E
Schoutens, A
Van Gansbeke, B
Albert, Adelin  ;  Université de Liège - ULiège > Département des sciences de la santé publique > Informatique médicale et biostatistique
Goffinet, Gerhard ;  Université de Liège - ULiège > Services généraux (Faculté des sciences) > Relations académiques et scientifiques (Sciences)
Camu, F
Legros, F J
Language :
English
Title :
Scintigraphic visualization of intrathecal liposome biodistribution.
Publication date :
1997
Journal title :
Acta Anaesthesiologica Scandinavica
ISSN :
0001-5172
eISSN :
1399-6576
Publisher :
Blackwell Munksgaard, Oxford, United Kingdom
Volume :
41
Issue :
1 Pt 1
Pages :
25-34
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 21 January 2013

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