SCINTIGRAPHIC VISUALIZATION OF INTRATHECAL LIPOSOME BIODISTRIBUTION

Background: Liposomes containing local anaesthetics have been administ ered 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 injec tion in rats by scintigraphic imaging during 24 h. Methods: We adminis tered Tc-99m-labeled multilamellar (MLV) and small unilamellar vesicle s (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 microscop y and of neurotoxic products from phosphatidylcholine hydrolysis and p eroxidation, both during the preparation process and after 24 h incuba tion in cerebrospinal fluid at 37 degrees C in vitro. Results: SUV imm ediately diffused from the lumbar site of injection to the head and we re cleared between 1 and 24 h after injection. MLV were cleared more s lowly from the spinal space and appeared in the head region 1 h after injection where they accumulated up to 24 h. These differences were ex plained in terms of vesicle sizes and volumes. SW with 0.05 mu m diame ters were rapidly absorbed into the blood through the arachnoid granul ations. In contrast, particles larger than the upper size limit of the arachnoid granulations permeability (+/-8 mu m) could accumulate in t he head with a slow elimination rate. Conclusion: This difference in c learance from the intrathecal space outlines the importance of definin g the size of the liposomes, the distribution of a tracer or a drug in side the liposomal preparation, the chemical stability and the absence of toxic degradation products of liposome formulations before clinica l use.