PDF(Pubmed)
Abstract：
Because of the blood-brain barrier (BBB), successful drug delivery to the brain has long been a key objective for the medical community, calling for pioneering technologies to overcome this challenge. Convection-enhanced delivery (CED), a form of direct intraparenchymal microinfusion, shows promise but requires optimal infusate design and real-time distribution monitoring. The size of the infused substances appears to be especially critical, with current knowledge being limited. Herein, we examined the intracranial administration of polyethylene glycol (PEG)-coated nanoparticles (NPs) of various sizes using CED in groups of healthy minipigs (n = 3). We employed stealth liposomes (LIPs, 130 nm) and two gold nanoparticle designs (AuNPs) of different diameters (8 and 40 nm). All were labeled with copper-64 for quantitative and real-time monitoring of the infusion via positron emission tomography (PET). NPs were infused via two catheters inserted bilaterally in the putaminal regions of the animals. Our results suggest CED with NPs holds promise for precise brain drug delivery, with larger LIPs exhibiting superior distribution volumes and intracranial retention over smaller AuNPs. PET imaging alongside CED enabled dynamic visualization of the process, target coverage, timely detection of suboptimal infusion, and quantification of distribution volumes and concentration gradients. These findings may augment the therapeutic efficacy of the delivery procedure while mitigating unwarranted side effects associated with nonvisually monitored delivery approaches. This is of vital importance, especially for chronic intermittent infusions through implanted catheters, as this information enables informed decisions for modulating targeted infusion volumes on a catheter-by-catheter, patient-by-patient basis.
摘要：
由于血脑屏障（BBB），成功将药物输送到大脑长期以来一直是医学界的关键目标，呼吁开拓性技术来克服这一挑战。对流增强递送(CED),一种直接实质内微输注的形式，显示出希望，但需要最佳的输液设计和实时分布监控。注入物质的大小似乎特别关键，目前的知识是有限的。在这里，我们在健康小型猪组中使用CED检查了不同大小的聚乙二醇(PEG)包被的纳米颗粒(NPs)的颅内给药情况(n=3).我们采用了隐形脂质体(LIP，130nm）和两个不同直径（8和40nm）的金纳米颗粒设计（AuNP）。全部用铜-64标记,用于通过正电子发射断层扫描(PET)定量和实时监测输注。NPs通过两侧插入动物卵皮区域的两个导管输注。我们的结果表明，带有NP的CED有望实现精确的脑部药物输送，与较小的AuNP相比，较大的LIP表现出优越的分布体积和颅内保留。PET成像与CED一起实现了过程的动态可视化，目标覆盖率,及时发现次优输液，以及分布体积和浓度梯度的量化。这些发现可能会增强递送程序的治疗功效，同时减轻与非视觉监测的递送方法相关的不必要的副作用。这是至关重要的,尤其是通过植入导管的慢性间歇性输注，由于这些信息能够在逐个导管的情况下做出明智的决定，以调节导管上的目标输注量，逐个患者的基础。
