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Nasal delivery of nanoliposome-encapsulated ferric ammonium citrate can increase the iron content of rat brain

Nasal delivery of nanoliposome-encapsulated ferric ammonium ...

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中国神经科学学会第十二届全国学术会议

作者： xue-Ling GUO Hong ZHENG Yue-Tong GUO Yan WANG Gregory J.ERSON Yun-Zhe CI Peng YU Lina GENG Yan-Zhong CHANG Laboratory of Molecular Iron Metabolism Key laboratory of Animal PhysiologyBiochemistry and Molecular Biology of Hebei Province College of Life Sciences Hebei Normal University College of Chemistry and Material Science Hebei Normal University

Background Iron deficiency in children can have significant neurological consequences, and iron supplementation is an effective treatment of choice. However, traditional routes of iron supplementation do not allow efficient iron delivery to the brain due to the presence of the blood-brain barrier. So an easily delivered iron formulation with high absorption efficiency potentially could find widespread application in iron deficient infants. Methods FAC nanoliposomes（FAC-LIP） were prepared with ethanol injection method, and then characterized with ultraviolet spectrophotometry, transmission electron microscopy and dynamic light scatting. After nasal delivery of FAC-LIP, the brain iron contents were detected with micro-x-ray fluorescence, inductively coupled plasma mass spectroscopy, western blotting method, and the side effects were examined with TUNEL, quantitative real-time PCR and biochemical analysis. Results In this study, we have developed and characterized a nanovesicular formulation of ferric ammonium citrate（ferric ammonium citrate nanoliposomes, FAC-LIP） and have shown that it can increase brain iron levels in rats following nasal administration. FAC was incorporated into liposomes with high efficiency（97%） and the liposomes were small（40 nm） and stable. Following intranasal delivery in rats, FAC-LIP significantly increased the iron content in the olfactory bulb, cerebral cortex, striatum, cerebellum and hippocampus, and was more efficient at doing so than FAC alone. No signs of apoptosis or abnormal cell morphology were observed in the brain following FAC-LIP administration, and there were no significant changes in the levels of SOD and MDA, except in the cerebellum and hippocampus. No obvious morphological changes were observed in lung epithelial cells or tracheal mucosa after nasal delivery, suggesting that the formulation was not overtly toxic. Conclusions In this study, nanoscale FAC-LIP proved an effective system delivering iron to the brain, with high

关键词： Nasal delivery FAC Nanoliposomes ICP-MS mmicro-x-ray fluorescence

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