Guo Xueling, Zheng Hong, Guo Yuetong, Wang Yan, Anderson Gregory J, Ci Yunzhe, Yu Peng, Geng Lina, Chang Yan-Zhong
Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Sciences, Hebei Normal University, Shijiazhuang, 050024, China.
College of Chemistry and Material Science, Hebei Normal University, 20, Nanerhuan Eastern Road, Shijiazhuang, 050024, Hebei, China.
J Nanobiotechnology. 2017 Jun 2;15(1):42. doi: 10.1186/s12951-017-0277-2.
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.
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.
In this study, nanoscale FAC-LIP proved an effective system delivering iron to the brain, with high encapsulation efficiency and low toxicity in rats. Our studies provide the foundation for more detailed investigations into the applications of niosomal nasal delivery of liposomal formulations of iron as a simple and safe therapy for iron deficiency anemia. Graphical abstract The diagrammatic sketch of "Nasal delivery of nanoliposome-encapsulated ferric ammonium citrate can increase the iron content of rat brain". Nanoliposome-encapsulated ferric ammonium citrate (FAC-LIP) was successfully prepared and intranasal administration of FAC-LIP increased both the total iron contents and iron storage protein (FTL) expression in rat olfactory bulb, cerebral cortex, striatum and hippocampus, compared with those of FAC groups. Moreover, there was not overtly toxic affects to brain, lung epithelial cells and tracheal mucosa.
儿童缺铁会产生严重的神经学后果，补充铁剂是一种有效的治疗选择。然而，由于血脑屏障的存在，传统的补铁途径无法使铁有效地输送到大脑。因此，一种易于递送且吸收效率高的铁制剂可能会在缺铁婴儿中得到广泛应用。
在本研究中，我们开发并表征了一种柠檬酸铁铵纳米囊泡制剂（柠檬酸铁铵纳米脂质体，FAC-LIP），并表明经鼻腔给药后它可提高大鼠脑内铁水平。FAC被高效地包封于脂质体中（97%），且脂质体体积小（40nm）且稳定。在大鼠经鼻给药后，FAC-LIP显著增加了嗅球、大脑皮层、纹状体、小脑和海马中的铁含量，且在这方面比单独使用FAC更有效。给予FAC-LIP后，大脑中未观察到凋亡迹象或细胞形态异常，超氧化物歧化酶（SOD）和丙二醛（MDA）水平除在小脑和海马中外无显著变化。经鼻给药后，肺上皮细胞或气管黏膜未观察到明显的形态学变化，表明该制剂无明显毒性。
在本研究中，纳米级的FAC-LIP被证明是一种将铁输送到大脑的有效系统，在大鼠中具有高包封效率和低毒性。我们的研究为更详细地研究基于铁脂质体制剂的非离子表面活性剂囊泡经鼻给药作为缺铁性贫血的一种简单安全疗法的应用奠定了基础。图形摘要“纳米脂质体包封的柠檬酸铁铵经鼻给药可增加大鼠脑内铁含量”的示意图。与FAC组相比，成功制备了纳米脂质体包封的柠檬酸铁铵（FAC-LIP），经鼻给予FAC-LIP增加了大鼠嗅球、大脑皮层、纹状体和海马中的总铁含量及铁储存蛋白（FTL）表达。此外，对脑、肺上皮细胞和气管黏膜无明显毒性作用。
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