Bergonzi Maria C, Guccione Clizia, Grossi Cristina, Piazzini Vieri, Torracchi Andrea, Luccarini Ilaria, Casamenti Fiorella, Bilia Anna R
Department of Chemistry, Building of Pharmaceutical Sciences, University of Florence, Via Ugo Schiff 6, 50019, Sesto Fiorentino, FI, Italy.
Department of Neuroscience, Psychology, Drug Research and Child Health, Division of Pharmacology and Toxicology, University of Florence, 50139, Florence, FI, Italy.
ChemMedChem. 2016 Aug 19;11(16):1840-9. doi: 10.1002/cmdc.201600080. Epub 2016 Mar 7.
Human serum albumin nanoparticles (NPs) have gained considerable attention owing to their high loading capacity for various drugs and the fact that they are well tolerated. The aim of this work was to investigate two different methods to produce NPs without the use of organic solvents and to obtain useful drug-delivery systems to cross the blood-brain barrier. NPs were obtained by coacervation, using both chemical and thermal cross-linking processes. They were developed and optimized to target brain tissues after parenteral administration in healthy rats. Furthermore, their distribution, cellular uptake, and fate were investigated in vivo after intracerebral injection in healthy rats. The toxicity of the developed carriers was estimated by behavioral tests. All NPs were chemically and physically characterized by dynamic light scattering, transmission electron microscopy, and high-performance liquid chromatography coupled with diode array and fluorimetric detectors. Their distribution and fate in the brain were evaluated by fluorescence microscopy. NPs were observed to be located in different brain tissues depending on the mode of injection, and did not induce an inflammatory response. Behavioral tests demonstrated no locomotor, explorative, or cognitive function impairment induced by the NPs.
人血清白蛋白纳米颗粒（NPs）因其对各种药物的高负载能力以及良好的耐受性而备受关注。这项工作的目的是研究两种不使用有机溶剂生产纳米颗粒的不同方法，并获得有用的药物递送系统以穿越血脑屏障。通过凝聚法获得纳米颗粒，采用化学和热交联过程。它们在健康大鼠经肠胃外给药后进行开发和优化，以靶向脑组织。此外，在健康大鼠脑内注射后，对其体内分布、细胞摄取和归宿进行了研究。通过行为测试评估所开发载体的毒性。所有纳米颗粒通过动态光散射、透射电子显微镜以及与二极管阵列和荧光检测器联用的高效液相色谱进行化学和物理表征。通过荧光显微镜评估它们在脑中的分布和归宿。观察到纳米颗粒根据注射方式位于不同的脑组织中，并且未引发炎症反应。行为测试表明纳米颗粒未引起运动、探索或认知功能损害。
