Center for Paralysis Research, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA.
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.
J Biol Eng. 2010 Jan 29;4(1):2. doi: 10.1186/1754-1611-4-2.
The highly reactive aldehyde acrolein is a very potent endogenous toxin with a long half-life. Acrolein is produced within cells after insult, and is a central player in slow and progressive "secondary injury" cascades. Indeed, acrolein-biomolecule complexes formed by cross-linking with proteins and DNA are associated with a number of pathologies, especially central nervous system (CNS) trauma and neurodegenerative diseases. Hydralazine is capable of inhibiting or reducing acrolein-induced damage. However, since hydralazine's principle activity is to reduce blood pressure as a common anti-hypertension drug, the possible problems encountered when applied to hypotensive trauma victims have led us to explore alternative approaches. This study aims to evaluate such an alternative - a chitosan nanoparticle-based therapeutic system.
Hydralazine-loaded chitosan nanoparticles were prepared using different types of polyanions and characterized for particle size, morphology, zeta potential value, and the efficiency of hydralazine entrapment and release. Hydralazine-loaded chitosan nanoparticles ranged in size from 300 nm to 350 nm in diameter, and with a tunable, or adjustable, surface charge.
We evaluated the utility of chitosan nanoparticles with an in-vitro model of acrolein-mediated cell injury using PC -12 cells. The particles effectively, and statistically, reduced damage to membrane integrity, secondary oxidative stress, and lipid peroxidation. This study suggests that a chitosan nanoparticle-based therapy to interfere with "secondary" injury may be possible.
具有长半衰期的高反应性醛丙烯醛是一种非常有效的内源性毒素。丙烯醛在细胞受到损伤后在细胞内产生，是缓慢和进行性“二次损伤”级联反应的核心参与者。事实上，通过与蛋白质和 DNA 交联形成的丙烯醛-生物分子复合物与许多病理学有关，特别是中枢神经系统（CNS）创伤和神经退行性疾病。肼屈嗪能够抑制或减少丙烯醛诱导的损伤。然而，由于肼屈嗪的主要作用是降低血压作为一种常见的抗高血压药物，因此在应用于低血压创伤患者时可能会遇到问题，这促使我们探索替代方法。本研究旨在评估一种替代方法 - 基于壳聚糖纳米粒子的治疗系统。
使用不同类型的聚阴离子制备了载有肼屈嗪的壳聚糖纳米粒子，并对其粒径、形态、Zeta 电位值以及肼屈嗪包封和释放的效率进行了表征。载有肼屈嗪的壳聚糖纳米粒子的直径在 300nm 至 350nm 之间，并且具有可调或可调节的表面电荷。
我们使用 PC-12 细胞的丙烯醛介导的细胞损伤体外模型评估了壳聚糖纳米粒子的实用性。这些颗粒有效地、统计学上减少了膜完整性、二次氧化应激和脂质过氧化损伤。这项研究表明，基于壳聚糖纳米粒子的治疗方法可能可以干扰“二次”损伤。
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