Voigt Nadine, Henrich-Noack Petra, Kockentiedt Sarah, Hintz Werner, Tomas Jürgen, Sabel Bernhard A
Institute of Medical Psychology, Otto-von-Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany.
Institute of Process Engineering, Otto-von-Guericke University, Universitätsplatz 2, 39106 Magdeburg, Germany.
J Nanopart Res. 2014 Jun 1;16(6). doi: 10.1007/s11051-014-2379-1. Epub 2014 May 6.
Polybutylcyanoacrylate nanoparticles (PBCA NPs) are candidates for a drug delivery system, which can cross the blood-brain barrier (BBB). Because little is known about their toxicity, we exposed cells to PBCA NPs in vitro and in vivo and monitored their life and death assays. PBCA NPs were fabricated with different surfactants according to the mini-emulsion technique. Viabilities of HeLa and HEK293 cells after NP incubation were quantified by analysing cellular metabolic activity (MTT-test). We then repetitively injected i.v. rhodamine-labelled PBCA NP variations into rats and monitored the survival and morphology of retrogradely labelled neurons by in vivo confocal neuroimaging (ICON) for five weeks. To test for carrier-efficacy and safety, PBCA NPs loaded with Kyotorphin were injected in rats, and a hot plate test was used to quantify analgesic effects. In vitro, we found dose-dependent cell death which was, however, only detectable at very high doses and mainly seen in the cultures incubated with NPs fabricated with the tensids SDS and Tween. However, the in vivo experiments did not show any NP-induced neuronal death, even with particles which were toxic at high dose in vitro, i.e. NPs with Tween and SDS. The increased pain threshold at the hot plate test demonstrated that PBCA NPs are able to cross the BBB and thus comprise a useful tool for drug delivery into the central nervous system (CNS). Our findings showing that different nanoparticle formulations are non-toxic have important implications for the value of NP engineering approaches in medicine.
聚氰基丙烯酸丁酯纳米颗粒（PBCA NPs）是一种药物递送系统的候选材料，它能够穿过血脑屏障（BBB）。由于对其毒性了解甚少，我们在体外和体内将细胞暴露于PBCA NPs中，并监测它们的生死检测。根据微乳液技术，用不同的表面活性剂制备了PBCA NPs。通过分析细胞代谢活性（MTT试验）来量化NP孵育后HeLa和HEK293细胞的活力。然后，我们将罗丹明标记的PBCA NP变体反复静脉注射到大鼠体内，并通过体内共聚焦神经成像（ICON）监测逆行标记神经元的存活和形态，持续五周。为了测试载体的有效性和安全性，将负载脑啡肽的PBCA NPs注射到大鼠体内，并使用热板试验来量化镇痛效果。在体外，我们发现了剂量依赖性细胞死亡，然而，这种现象只有在非常高的剂量下才能检测到，并且主要出现在与用表面活性剂十二烷基硫酸钠（SDS）和吐温制备的NP孵育的培养物中。然而，体内实验并未显示任何NP诱导的神经元死亡，即使是在体外高剂量下有毒的颗粒，即含有吐温和SDS的NP。热板试验中疼痛阈值的升高表明PBCA NPs能够穿过血脑屏障，因此是一种将药物递送至中枢神经系统（CNS）的有用工具。我们的研究结果表明不同的纳米颗粒制剂无毒，这对医学中NP工程方法的价值具有重要意义。
