ARPA Calabria, Environmental Epidemiology Centre, CNR-ISN Section of Pharmacology, Complesso Ninì Barbieri, I-88021 Roccelletta di Borgia (CZ), Italy.
Neurosci Lett. 2010 Jan 18;469(1):93-6. doi: 10.1016/j.neulet.2009.11.051. Epub 2009 Nov 26.
The purpose of this investigation was to explore the potentiality of a novel animal model to be used for the in vivo evaluation of the ability of a drug delivery system to promote the passage through the blood-brain barrier (BBB) and/or to improve the brain localization of a bioactive compound. A Tween 80-coated poly-L-lactid acid nanoparticles was used as a model of colloidal drug delivery system, able to trespass the BBB. Tacrine, administered in LiCl pre-treated rats, induces electrocorticographic seizures and delayed hippocampal damage. The toxic effects of tacrine-loaded poly-L-lactid acid nanoparticles (5mg/kg), a saline solution of tacrine (5mg/kg) and an empty colloidal nanoparticle suspension were compared following i.p. administration in LiCl-pre-treated Wistar rats. All the animals treated with tacrine-loaded nanoparticles showed an earlier outcome of CNS adverse symptoms, i.e. epileptic onset, with respect to those animals treated with the free compound (10 min vs. 22 min respectively). In addition, tacrine-loaded nanoparticles administration induced damage of neuronal cells in CA1 field of the hippocampus in all treated animals, while the saline solution of tacrine only in 60% of animals. Empty nanoparticles provided similar results to control (saline-treated) group of animals. In conclusion, the evaluation of time-to-onset of symptoms and the severity of neurodegenerative processes induced by the tacrine-lithium model of epilepsy in the rat, could be used to evaluate preliminarily the capability of a drug delivery system to trespass (or not) the BBB in vivo.
本研究旨在探索一种新型动物模型，用于评估药物传递系统促进药物通过血脑屏障（BBB）的能力和/或提高生物活性化合物脑内定位的潜能。聚乳酸纳米粒用聚山梨酯 80 包裹，作为胶态药物传递系统的模型，能够穿透 BBB。三羟甲基氨基甲烷（tacrine）在氯化锂预处理的大鼠中给药会引起脑电癫痫发作和海马延迟性损伤。用氯化锂预处理的 Wistar 大鼠腹腔注射给予三羟甲基氨基甲烷负载的聚乳酸纳米粒（5mg/kg）、三羟甲基氨基甲烷生理盐水溶液（5mg/kg）和空胶体纳米粒混悬液后，比较其毒性作用。与用游离化合物治疗的动物（分别为 10 分钟和 22 分钟）相比，所有用载有三羟甲基氨基甲烷的纳米粒治疗的动物均更早出现中枢神经系统不良反应症状，即癫痫发作。此外，载有三羟甲基氨基甲烷的纳米粒给药会导致所有治疗动物的海马 CA1 区神经元细胞损伤，而三羟甲基氨基甲烷生理盐水溶液仅在 60%的动物中引起损伤。空纳米粒与生理盐水处理的对照组动物的结果相似。总之，用三羟甲基氨基甲烷-氯化锂癫痫大鼠模型评估症状发作时间和神经退行性过程的严重程度，可用于初步评估药物传递系统在体内穿透 BBB 的能力。
