Variables affecting convection-enhanced delivery to the striatum: a systematic examination of rate of infusion, cannula size, infusate concentration, and tissue-cannula sealing time
Variables affecting convection-enhanced delivery to the striatum: a systematic examination of rate of infusion, cannula size, infusate concentration, and tissue-cannula sealing time
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DOI：
10.3171/jns.1999.90.2.0315
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发表时间：
1999-02-01
影响因子：
4.1
通讯作者：
Oldfield, EH
中科院分区：
文献类型：
--
作者：
Chen, MY;Lonser, RR;Oldfield, EH
对象。虽然最近的研究表明，对流可以用于在临床上显著的体积上均匀地、有针对性地分布中枢神经系统（CNS）内的大分子，并且输注的体积和目标位置（灰质而不是白质）影响分布，但对可能影响对流增强分布的最佳使用的其他因素知之甚少。为了更充分地了解影响对流输送的变量，我们检查了输注速度、输送套管大小、输注浓度和输注前密封时间。采用对流输送法将4 μ l的c -14白蛋白送入40只大鼠纹状体。采用定量放射自显像、美国国立卫生研究院图像分析软件、闪烁分析和组织学分析，观察输注速率（0.1、0.5、1和5 μ l/min）、插管尺寸（32、28和22 μ l）、输注浓度（100%、50%和25%）和输注前密封时间（0和70 min）对对流输送的影响。较高的输注率（1和5 μ l/min）与较低的输注率（0.1 μ l/min[4 +/- 3.6%]和0.5 μ l/min[5.2 +/- 3.6%]）相比，输注率（22.7 +/- 11.7%和30.3 +/- 7.8%[平均+/-标准差]）显著增加（p < 0.05）。注射速率为0.1 μ l/min时，输液回收率（95.1 +/- 2.8%）显著高于注射速率较高时（85.2 +/- 4%）（p < 0.05）。使用大管（28和22口径）比使用小管（32口径[5.2 +/- 3.6%]）产生更多的漏回（分别为35.7 +/- 8.1%和21.1 +/- 7.5%），差异有统计学意义（p < 0.05）。改变输注液浓度和预封注时间对输注液的体积分布、区域分布和输注回收率没有影响。在该小动物模型中，注射速率和插管大小对分子对流分布有显著影响，而注射前封闭时间和注射浓度变化对分子对流分布无影响。了解影响中枢神经系统内对流输送的参数可用于在实验环境中增强潜在治疗剂的输送，并指出在临床环境中最佳使用该方法进行药物输送时需要考虑的变量。
Object. Although recent studies have shown that convection can be used to distribute macromolecules within the central nervous system (CNS) in a homogeneous, targeted fashion over clinically significant volumes and that the volume of infusion and target location (gray as opposed to white matter) influence distribution, little is known about other factors that may influence optimum use of convection-enhanced distribution. To understand the variables that affect convective delivery more fully, we examined the rate of infusion, delivery cannula size, concentration of infusate, and preinfusion sealing time.Methods. The authors used convection to deliver 4 mu l of C-14-albumin to the striatum of 40 rats. The effect of the rate of infusion (0.1, 0.5, 1, and 5 mu l/minute), cannula size (32, 28, and 22 gauge), concentration of infusate (100%, 50%, and 25%), and preinfusion sealing time (0 and 70 minutes) on convective delivery was examined using quantitative autoradiography, National Institutes of Health image analysis software, scintillation analysis, and histological analysis.Higher rates of infusion (1 and 5 mu l/minute) caused significantly (p < 0.05) more leakback of infusate (22.7 +/- 11.7% and 30.3 +/- 7.8% [mean +/- standard deviation], respectively) compared with lower rates (0.1 mu l/minute [4 +/- 3.6%] and 0.5 mu l/minute [5.2 +/- 3.6%]). Recovery of infusate was significantly (p < 0.05) higher at the infusion rate of 0.1 mu l/minute (95.1 +/- 2.8%) compared with higher rates (85.2 +/- 4%). The use of large cannulae (28 and 22 gauge) produced significantly (p < 0.05) more leakback(35.7 +/- 8.1% and 21.1 +/-: 7.5%, respectively) than the smaller cannula (32 gauge [5.2 +/- 3.6%]). Varying the concentration of the infusate and the preinfusion sealing time did not alter the volume of distribution, regional distribution, or infusate recovery.Conclusions. Rate of infusion and cannula size can significantly affect convective distribution of molecules, whereas preinfusion sealing time and variations in infusate concentration have no effect in this small animal model. Understanding the parameters that influence convective delivery within the CNS can be used to enhance delivery of potentially therapeutic agents in an experimental setting and to indicate the variables that will need to be considered for optimum use of this approach for drug delivery in the clinical setting.