Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
J Drug Target. 2011 Sep;19(8):637-46. doi: 10.3109/1061186X.2010.523789. Epub 2010 Oct 14.
Clioquinol (CQ), a metal chelator, has gained renewed attention due to its ability to modulate metal homeostasis in neurodegenerative disorders such as Alzheimer's disease.
To investigate the protective effects of a wide range of concentrations of CQ on two human neuroblastoma cell lines (IMR-32 and SKN-AS) and to develop and characterize a new controlled release system of CQ consisting of biodegradable microspheres.
H(2)O(2) (400 μM) adequately induced death cell in IMR-32 and SKN-AS cell lines thereby resulting in a useful model for neuroprotective studies. CQ (20-50 μM) induced a potent and robust protective effect against peroxide-mediated oxidative stress in human neuronal-like cells (SKN-AS) determined by both MTT and flow cytometry (cell viability). These results were also confirmed by means of reactive oxygen species (ROS) production. Biodegradable poly(dl-lactic-co-glycolic acid) (PLGA) resomers assayed for microspheres preparation were PLGA-502 and PLGA-502H. Optimization by using an experimental design resulted in a formulation prepared with CQ (112 mg) and PLGA-502H (400 mg). With this formulation, mean encapsulation efficiency of 82.37% ± 6.67% and, zero-order release rate of 58 ± 3µg CQ/day/10 mg microspheres between Days 10 and 35 were obtained.
We have developed a promising formulation for the treatment of Alzheimer's disease.
弹性蛋白酶（CQ），一种金属螯合剂，由于其能够调节神经退行性疾病（如阿尔茨海默病）中的金属内稳态，因此重新受到关注。
研究广泛浓度的 CQ 对两种人神经母细胞瘤细胞系（IMR-32 和 SKN-AS）的保护作用，并开发和表征由可生物降解微球组成的 CQ 新的控释系统。
H ₂ O ₂ （400 μM）充分诱导了 IMR-32 和 SKN-AS 细胞系中的死亡细胞，从而为神经保护研究提供了有用的模型。 CQ（20-50 μM）在人神经样细胞（SKN-AS）中诱导出强大的保护性作用，可通过 MTT 和流式细胞术（细胞活力）来确定，以抵抗过氧化物介导的氧化应激。通过活性氧（ROS）的产生也证实了这些结果。可生物降解的聚（DL-丙交酯-共-乙交酯）（PLGA）用于微球制备的树脂被测定为 PLGA-502 和 PLGA-502H。通过实验设计进行优化，得到了一种含有 CQ（112 mg）和 PLGA-502H（400 mg）的制剂。该制剂的平均包封效率为 82.37%±6.67%，并且在第 10 天至第 35 天之间以零级释放速率 58±3μg CQ/天/10mg 微球释放。
我们已经开发出一种有前途的阿尔茨海默病治疗制剂。
