Umbrain V, D'Haese J, Alafandy M, De Roover E, Schoutens A, Van Gansbeke B, Albert A, Goffinet G, Camu F, Legros F J
Department of Anaesthesiology, Flemish Free University of Brussels Medical Centre, Belgium.
Acta Anaesthesiol Scand. 1997 Jan;41(1 Pt 1):25-34. doi: 10.1111/j.1399-6576.1997.tb04609.x.
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.
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.
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.
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.
含有局部麻醉剂的脂质体已被鞘内注射和硬膜外给药。作为药物载体的脂质体的药代动力学一直未得到充分关注。因此，我们通过闪烁成像观察了大鼠鞘内注射脂质体后24小时内的生物分布情况。
我们将具有特定大小和体积分散度的99mTc标记的多层脂质体（MLV）和小单层脂质体（SUV）注入腰椎水平的脑脊液中。通过光学和电子显微镜观察，这些脂质体在制备过程中以及在37℃脑脊液中体外孵育24小时后，均未受到放射性标记胶体的污染，也未受到磷脂酰胆碱水解和过氧化产生的神经毒性产物的污染。
SUV立即从注射部位的腰部扩散到头部，并在注射后1至24小时内清除。MLV从脊髓腔清除得较慢，注射后1小时出现在头部区域，并在那里积聚长达24小时。这些差异可以用囊泡的大小和体积来解释。直径为0.05微米的SUV通过蛛网膜颗粒迅速吸收到血液中。相比之下，大于蛛网膜颗粒通透性上限（±8微米）的颗粒可以在头部积聚，清除率较慢。
鞘内空间清除率的这种差异凸显了在临床使用前确定脂质体大小、脂质体制剂内示踪剂或药物分布、化学稳定性以及脂质体制剂无有毒降解产物的重要性。
