阿魏酸(Fer)和香叶醇(Ger)是天然化合物,其抗氧化和抗炎活性赋予有益的特性,如抗菌,抗癌,和神经保护作用。然而,常规给药后,这些化合物的短半衰期损害了它们的治疗活性。我们提议,因此,一种新的前药(Fer-Ger),通过Fer和Ger的生物催化酯缀合获得,以增强设计为Fer-Ger递送和靶向系统的固体脂质微粒(SLM)的负载。SLM是通过不含有机溶剂的热乳液技术获得的。HPLC-UV分析表明,Fer-Ger在人或大鼠全血和大鼠肝匀浆中水解,半衰期分别为193.64±20.93、20.15±0.75和3.94±0.33min,分别,但不是在大鼠大脑匀浆中。与活性氧(ROS)诱导剂H2O2孵育的神经元分化小鼠神经母细胞瘤N2a细胞的研究证明了Fer-Ger预防氧化损伤的能力,尽管它似乎促进了ROS。包封在三硬脂酸甘油酯SLM中的Fer-Ger的量,在不存在或存在葡萄糖的情况下获得,为1.5±0.1%,允许控制前药释放(葡萄糖不存在)或敏感地提高其水溶解速率(葡萄糖存在)。这些新的“绿色”载体可以潜在地延长Fer和Ger的有益作用,或作为鼻用制剂诱导神经保护。
Ferulic acid (Fer) and geraniol (Ger) are natural compounds whose antioxidant and anti-inflammatory activity confer beneficial properties, such as antibacterial, anticancer, and neuroprotective effects. However, the short half-lives of these compounds impair their therapeutic activities after conventional administration. We propose, therefore, a new
prodrug (Fer-Ger) obtained by a bio-catalyzed ester conjugation of Fer and Ger to enhance the loading of solid lipid microparticles (SLMs) designed as Fer-Ger delivery and targeting systems. SLMs were obtained by hot emulsion techniques without organic solvents. HPLC-UV analysis evidenced that Fer-Ger is hydrolyzed in human or rat whole blood and rat liver homogenates, with half-lives of 193.64 ± 20.93, 20.15 ± 0.75, and 3.94 ± 0.33 min, respectively, but not in rat brain homogenates. Studies on neuronal-differentiated mouse neuroblastoma N2a cells incubated with the reactive oxygen species (ROS) inductor H2O2 evidenced the Fer-Ger ability to prevent oxidative injury, despite the fact that it appears ROS-promoting. The amounts of Fer-Ger encapsulated in tristearin SLMs, obtained in the absence or presence of glucose, were 1.5 ± 0.1%, allowing the control of the
prodrug release (glucose absence) or to sensibly enhance its water dissolution rate (glucose presence). These new \"green\" carriers can potentially prolong the beneficial effects of Fer and Ger or induce neuroprotection as nasal formulations.